Affinage

RAC1

Ras-related C3 botulinum toxin substrate 1 · UniProt P63000

Length
192 aa
Mass
21.4 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAC1 is a Rho-family small GTPase that cycles between GDP-bound and GTP-bound states to orchestrate actin-dependent membrane remodeling, cell polarity, migration, survival, and lineage-specific transcriptional programs (PMID:10934035, PMID:29141223, PMID:31422887). Its activity is set spatially: GTP-loaded Rac1 partitions into plasma-membrane nanoclusters through its polybasic tail engaging PIP2/PIP3 (PMID:29141223), and transient effector-dependent immobilizations at the lamellipodium tip drive WAVE regulatory complex (WRC)-dependent actin branching and membrane protrusion, a process locally restrained by the Rac1-binding suppressor CYRI/Fam49, which limits Scar/WAVE recruitment (PMID:30054448, PMID:31422887). Active Rac1 also captures microtubule plus-ends for polarization by forming a Rac1–IQGAP1–CLIP-170 complex, and IQGAP1 binding both sustains GTP-loading and, for non-prenylated Rac1, routes it to ubiquitin-dependent degradation (PMID:12110184, PMID:17984089, PMID:31484924, PMID:32783108). Rac1 activity is controlled by GEFs (Sos1, Vav/Vav2, DOCK2, alsin, Tiam1, β-PIX), GAPs (α1-/β2-chimaerin, centralspindlin CYK4, bacterial SptP and YopE), caveolin-1-promoted ubiquitin-dependent degradation, geranylgeranylation that restrains effector engagement, and Cys18 glutathiolation that promotes nucleotide exchange (PMID:10499590, PMID:22945935, PMID:16520382, PMID:30446664, PMID:12393632, PMID:25289457, PMID:16802292, PMID:31484924, PMID:7534315). Downstream, Rac1 engages PAK to regulate c-Myc-dependent epidermal stem cell fate, controls NADPH oxidase by promoting gp91phox–p67phox assembly, supports PI3K-dependent survival/anoikis resistance, and acts in the nucleus with Tiam1 and RORγt to activate the Il17a promoter (PMID:16081735, PMID:16651530, PMID:27725632, PMID:11369774). Genetic studies establish non-redundant, isoform-specific roles in hematopoietic stem cell engraftment, Schwann cell myelination, chondrogenesis, axon growth, synaptic plasticity, and cardiac hypertrophy (PMID:14564009, PMID:16081735, PMID:16651530, PMID:23197717, PMID:32533921). Beyond these characterized axes, the corpus does not establish a unifying structural model of Rac1 nanocluster assembly.

Mechanistic history

Synthesis pass · year-by-year structured walk · 46 steps
  1. 1994 Medium

    Established that GAP-driven inactivation of Rac1 is a negative regulator of actin cytoskeletal architecture, defining the functional consequence of switching Rac1 off.

    Evidence Stable α1-chimaerin expression with in-extract Rac1 GAP assay and actin/vinculin/adhesion phenotyping in NIH3T3 cells

    PMID:7534315

    Open questions at the time
    • Single GAP studied; spatial control of GAP action not addressed
    • Effectors linking Rac1 to stress fibers/adhesion not identified here
  2. 1996 Medium

    Placed Rac1 as an obligate effector linking the Vav GEF to the JNK/SAPK kinase cascade and oncogenic transformation, connecting Rac1 to stress-kinase signaling.

    Evidence Dominant-negative Rac1 N17 epistasis with JNK/SAPK kinase assay and focus formation in COS-7/NIH3T3

    PMID:8760286

    Open questions at the time
    • Intermediate kinases between Rac1 and JNK not defined
    • Dominant-negative approach cannot exclude effects on related GTPases
  3. 1996 High

    Demonstrated conformation-specific Rac1 binding to tubulin requiring the active state but not GTP hydrolysis, an early link between Rac1 and the microtubule system.

    Evidence GTP-overlay binding, purified tubulin reconstitution, and effector-domain (D38A) plus GTPase-dead mutagenesis

    PMID:8631991

    Open questions at the time
    • Cellular relevance of direct tubulin binding not established
    • Relationship to IQGAP1/CLIP-170 microtubule capture unresolved
  4. 1997 High

    Showed Rac1 is required for FcγR-mediated phagocytosis acting downstream of F-actin recruitment, distinguishing actin nucleation from membrane remodeling.

    Evidence Dominant-negative Rac1 N17 with F-actin staining and phagocytosis assays in macrophages

    PMID:9348306

    Open questions at the time
    • Effectors mediating membrane remodeling not identified
    • Mechanism of cup closure unresolved
  5. 1998 High

    Refined the phagocytic role by showing Rac1 and Cdc42 perform distinct membrane/actin functions and coordinate phosphotyrosine resolution around particles.

    Evidence Stable dominant-negative Rac1/Cdc42 lines with morphology and phosphotyrosine imaging in RBL-2H3 mast cells

    PMID:9799231

    Open questions at the time
    • Molecular basis of the Rac1-vs-Cdc42 morphological divergence not defined
  6. 1998 High

    Defined the Rac1 polybasic C-terminus as a GTP-independent docking site for lipid kinases, linking Rac1 to local phosphoinositide metabolism and RhoGDI handoff.

    Evidence In vitro binding with Rac1 chimeras/peptides, co-purification, and RhoGDI co-IP

    PMID:9447972

    Open questions at the time
    • Functional output of the lipid-kinase complex on Rac1 signaling not tested
    • Single-lab biochemistry
  7. 1999 High

    Showed a bacterial effector (SptP) directly inactivates Rac1 as a GAP, providing biochemical proof that GTP hydrolysis reverses Rac1-driven cytoskeletal changes.

    Evidence In vitro GAP assay with purified SptP and Rac1/Cdc42 plus cellular phenotypic rescue

    PMID:10499590

    Open questions at the time
    • Host GAP equivalents not addressed here
  8. 2000 High

    Established that membrane recruitment of active Rac1 alone suffices for actin polymerization and internalization, and that effector binding (F37 loop) is essential.

    Evidence Rapamycin-inducible membrane recruitment with effector-loop mutagenesis and bead internalization

    PMID:10934035

    Open questions at the time
    • Identity of the essential effector not pinned down in this system
  9. 2001 Medium

    Identified PI3K as the survival-relevant branch downstream of active Rac1 in anoikis resistance, separating survival from ERK/p38/NF-κB outputs.

    Evidence Rac1-V12 expression in suspended MDCK cells with caspase/DNA-fragmentation readouts and pathway inhibitors

    PMID:11369774

    Open questions at the time
    • Direct Rac1–PI3K link mechanism not shown
    • Gain-of-function only
  10. 2002 High

    Defined the Rac1/Cdc42–IQGAP1–CLIP-170 tripartite complex that captures microtubule plus-ends to establish a single leading edge, connecting Rac1 to polarity.

    Evidence Reciprocal co-IP, GFP live imaging, and IQGAP1 binding-mutant expression in fibroblasts

    PMID:12110184

    Open questions at the time
    • How active Rac1 is spatially restricted to one edge not resolved here
  11. 2003 High

    Genetically resolved non-redundant Rac1-vs-Rac2 functions, assigning HSC/progenitor retention and engraftment to Rac1 and oxidase/migration to Rac2.

    Evidence Conditional single and double Rac1/Rac2 knockouts with transplantation, oxidase, and migration assays in mice

    PMID:14564009

    Open questions at the time
    • Molecular basis of isoform specificity not defined
  12. 2005 High

    Placed Rac1 upstream of PAK2 and c-Myc in epidermal stem cell fate, showing Rac1 restrains stem-cell differentiation.

    Evidence Inducible epidermal Rac1 KO with BrdU, c-Myc/PAK2 staining and epistasis in mice

    PMID:16081735

    Open questions at the time
    • Direct PAK2 substrate driving c-Myc regulation not identified
  13. 2005 Medium

    Showed Rac1/Cdc42 drive chondrocyte hypertrophy and apoptosis via p38 MAPK, antagonizing RhoA, linking Rac1 to skeletal cell-fate transitions.

    Evidence Gain-of-function plus p38 inhibitor epistasis with reporter, TUNEL, and phospho-p38 in chondrocytes

    PMID:15883643

    Open questions at the time
    • Endogenous Rac1 requirement not genetically tested here
    • Single lab
  14. 2005 Medium

    Demonstrated bacterial YopE/YopT generate spatially distinct Rac1 pools, revealing membrane vs cytoplasmic/nuclear Rac1 activation states.

    Evidence FRET Rac1 biosensor imaging during infection with YopE/YopT mutant Yersinia

    PMID:16228016

    Open questions at the time
    • Nuclear Rac1 GEFs not identified
    • Single-lab live-imaging study
  15. 2006 High

    Connected Rac1 to cardiac NADPH oxidase by showing Rac1 is required for gp91phox–p67phox assembly and angiotensin-II-induced hypertrophy.

    Evidence Cardiomyocyte-specific Rac1 KO with oxidase co-IP, activity, ROS, and echocardiography

    PMID:16651530

    Open questions at the time
    • Direct Rac1 contact within the oxidase complex not mapped here
  16. 2006 High

    Defined a p66shc–Sos1–Eps8–E3b1 module that enhances Rac1-specific GEF activity and oxidative stress, linking Rac1 activation to redox signaling.

    Evidence In vitro GEF assay, reciprocal co-IP, CH2 domain mapping, and Rac1-GTP pulldown

    PMID:16520382

    Open questions at the time
    • Physiological trigger of this module not defined here
  17. 2006 Medium

    Identified DGKγ as an upstream catalytic suppressor of Rac1 controlling lamellipodia, expanding lipid control of Rac1.

    Evidence DGKγ kinase-dead/active mutants, co-IP, dominant-negative Rac1 epistasis, and activation assays

    PMID:15102830

    Open questions at the time
    • GEF/GAP intermediary between DGKγ and Rac1 not defined
    • Single lab
  18. 2006 Medium

    Established alsin as a Rac1 GEF supporting motoneuron survival and axon growth, with Rac1 (not Rab5) as the relevant effector.

    Evidence Alsin siRNA with dominant-negative/active Rac1 and Rab5 rescue in motoneurons

    PMID:16802292

    Open questions at the time
    • Downstream survival effectors not identified
    • Single lab
  19. 2006 Medium

    Showed both loss and gain of Rac1 activity drive premature senescence via ROS and p53, identifying a homeostatic Rac1 activity window.

    Evidence Rac1-targeted and L61Rac1 MEFs with ROS, γH2AX, p53 phosphorylation, and p53-deletion epistasis

    PMID:17032649

    Open questions at the time
    • ROS source linking Rac1 to p53 not defined here
    • Single lab
  20. 2006 Medium

    Placed β-PIX downstream of ILK and upstream of Rac1 in integrin-mediated spreading, defining an adhesion-coupled activation route.

    Evidence ILK–PKL–β-PIX co-IP, dominant-negative β-PIX and siRNA epistasis, Rac1-GTP pulldown

    PMID:16723384

    Open questions at the time
    • Direct β-PIX nucleotide exchange on Rac1 not isolated here
    • Single lab
  21. 2007 High

    Mapped Rac1 switch-region determinants (Asp63/Arg68/Leu70, residues 32/36) that distinguish IQGAP1 binding from Cdc42 and partially overlap GAP sites.

    Evidence Systematic Rac1/Cdc42 mutagenesis with quantitative binding and competition assays

    PMID:17984089

    Open questions at the time
    • In-cell consequences of selective interface mutations not tested here
  22. 2007 Medium

    Showed Rac1 promotes chondrogenesis and N-cadherin/Sox9 expression, extending its role to mesenchymal differentiation.

    Evidence Pharmacologic inhibition, dominant-active overexpression, and conditional KO micromass cultures with RT-PCR/immunoblot

    PMID:17573353

    Open questions at the time
    • Effector pathway from Rac1 to Sox9 not defined
    • Single lab
  23. 2008 Medium

    Identified a β-PIX–Rac1 module mediating NOD2 membrane trafficking and negative feedback via Erbin in innate immune signaling.

    Evidence Rac1 activation assay, NOD2–β-PIX–Rac1 co-IP, siRNA, and NOD2 localization/NF-κB readouts

    PMID:18684957

    Open questions at the time
    • Whether Rac1 GTP-loading is required vs scaffolding not separated
    • Single lab
  24. 2009 Medium

    Defined gp130/Stat3 as an essential effector axis downstream of active Rac1 driving migration and proliferation.

    Evidence Rac1-V12 expression with gp130 siRNA, Stat3 reporter, and proliferation/migration assays

    PMID:19852956

    Open questions at the time
    • Mechanism of Rac1-induced IL-6 upregulation not defined
    • Gain-of-function only
  25. 2009 Medium

    Linked Rac1 to transcriptional derepression by showing PAK1 phosphorylates and inactivates BCL-6, with isoform-selective behavior of Rac1 vs Rac1b.

    Evidence Active Rac1 mutants, NSC23766 inhibition, BCL-6 fractionation, and in vitro PAK1 kinase assay on BCL-6

    PMID:19487462

    Open questions at the time
    • Endogenous physiological context of BCL-6 regulation not tested
    • Single lab
  26. 2009 Medium

    Showed CCK activates Rac1 through cooperative Gα13/Gαq signaling independent of PLC, defining a GPCR route to Rac1 in acinar cells.

    Evidence Active Gα constructs, RGS inhibitors, and Rac1/RhoA activation assays

    PMID:19940064

    Open questions at the time
    • GEF coupling Gα proteins to Rac1 not identified
    • Single lab
  27. 2010 High

    Revealed a non-canonical termination mechanism in which caveolin-1 directs ubiquitin-proteasomal degradation of GTP-bound Rac1 in an adhesion-dependent manner.

    Evidence Cav1 co-IP, Cav1-KO fibroblasts, ubiquitylation assay, and ubiquitylation-deficient Rac1 mutant

    PMID:20460433

    Open questions at the time
    • E3 ligase responsible for Rac1 ubiquitylation not identified here
  28. 2011 Medium

    Demonstrated high-affinity Rac1–calmodulin binding via the polybasic/prenyl region controls ARF6-dependent clathrin-independent endocytosis and PIP5K recruitment.

    Evidence Binding measurements, CaM inhibition, active/inactive Rac1 mutants, and PI4,5P2 tubulation/endocytosis assays

    PMID:21883766

    Open questions at the time
    • Physiological cargo of this endocytic route not defined
    • Single lab
  29. 2011 Medium

    Placed mTOR–S6K1 upstream of Rac1 in platelet spreading via an S6K1–Rac1–TIAM1 complex independent of Src/FAK.

    Evidence Co-IP of the tricomplex with mTOR/S6K1/Src/FAK inhibitor epistasis and spreading assays

    PMID:21757621

    Open questions at the time
    • Whether S6K1 acts catalytically on the GEF not resolved
    • Single lab
  30. 2011 Medium

    Resolved sequential Rap1→Rac1 signaling with Rac1 positive feedback onto Rap1, defining two Rac1 pools in platelet activation.

    Evidence EHT1864 inhibition, CalDAG-GEFI/P2Y12 double-KO mice, activation assays, and clot retraction

    PMID:22075250

    Open questions at the time
    • GEFs defining the two Rac1 pools not separately identified
    • Single lab
  31. 2012 High

    Established CYK4/centralspindlin as a Rac1-specific GAP that spatially segregates adhesion (ARHGEF7/PAK1) from the contractile ring during cytokinesis.

    Evidence In vitro GAP assay, GAP-mutant expression, and ARHGEF7/PAK1 depletion rescue with cytokinesis phenotyping

    PMID:22945935

    Open questions at the time
    • How CYK4 GAP activity is spatially confined to the equator not fully resolved
  32. 2012 High

    Identified a nuclear Tiam1/Rac1/RORγt complex that activates the Il17a promoter, giving Rac1 a direct transcriptional role in Th17 immunity.

    Evidence Co-IP, ChIP at Il17, T-cell-specific Rac1 KO, EAE model, and pharmacologic inhibition

    PMID:27725632

    Open questions at the time
    • How nuclear Rac1 is recruited/retained not defined
  33. 2012 Medium

    Showed Wnt3a activates Rac1 through CK1-dependent p120-catenin release from E-cadherin enabling a p120/Vav2/Rac1 complex, linking cadherin junctions to Rac1.

    Evidence Co-IP of p120/Vav2/Rac1, phosphorylation dissection, and Xenopus depletion/rescue

    PMID:22946057

    Open questions at the time
    • Direct catalytic step of Vav2 on Rac1 in this complex not isolated
    • Single lab
  34. 2012 High

    Demonstrated Rac1 is required for Schwann cell myelination acting upstream of PAK, NF2/merlin, and cAMP, with genetic and pharmacologic rescue.

    Evidence Conditional Rac1 KO, phospho-PAK/merlin immunoblots, NF2 mutant rescue, and rolipram rescue in mice

    PMID:23197717

    Open questions at the time
    • How Rac1 lowers cAMP mechanistically not defined
  35. 2013 High

    Showed GluN3A-NMDARs sequester GIT1 to limit β-PIX/Rac1/PAK signaling and spine growth, an activity-regulated brake on Rac1 in synapses.

    Evidence GluN3A–GIT1 co-IP, KO mice, shRNA, Rac1 activation assay, and spine morphology

    PMID:24297929

    Open questions at the time
    • Structural basis of GluN3A–GIT1 competition with β-PIX not defined
  36. 2014 High

    Identified Cys18 glutathiolation as a redox switch that promotes Rac1 nucleotide exchange and activation, linking oxidative state to GTP-loading.

    Evidence Mass spectrometry, in vitro nucleotide exchange on oxidized Rac1, pKa measurement, and C18 mutants with cellular validation

    PMID:25289457

    Open questions at the time
    • Physiological oxidant source for endogenous Cys18 modification not pinned
  37. 2017 Medium

    Defined Rac1 plasma-membrane nanoclusters formed via polybasic-tail/PIP2-PIP3 binding and enriched in protrusions, establishing spatial nanodomain organization of Rac1 signaling.

    Evidence Single-molecule tracking and super-resolution imaging with lipid perturbation

    PMID:29141223

    Open questions at the time
    • Compositional census of nanocluster effectors incomplete
    • Single lab
  38. 2018 High

    Showed Rac1 spatial gradients are shaped by localized GEF/GAP activity—specifically β2-chimaerin at the tip—rather than transport, controlling migration speed.

    Evidence Optogenetic GEF recruitment, FRET biosensors, micropatterning, and β2-chimaerin KO/depletion

    PMID:30446664

    Open questions at the time
    • Feedback wiring localizing β2-chimaerin not fully resolved molecularly
  39. 2018 High

    Identified CYRI/Fam49 as a Rac1-binding suppressor of Scar/WAVE that limits protrusion size and tunes chemotaxis and polarity.

    Evidence DUF1394–Rac1 binding, CYRI KO/overexpression, optogenetic Rac1 activation, and Scar/WAVE imaging

    PMID:30054448

    Open questions at the time
    • How CYRI competes with WRC at the molecular interface not fully mapped
  40. 2018 Medium

    Showed postsynaptic α2δ-1 is required and sufficient for thrombospondin-induced synaptogenesis via Rac1, linking a synaptogenic cue to Rac1.

    Evidence Cell-type-specific α2δ-1 KO, Rac1 activation assay, EM, and in vivo spine counts

    PMID:30054448

    Open questions at the time
    • GEF coupling α2δ-1 to Rac1 not identified
    • Single lab
  41. 2019 High

    Established that prenylation by GGTase-I restrains Rac1, with non-prenylated Rac1 binding IQGAP1 to drive exchange and degradation and to fuel inflammation.

    Evidence Rac1+/- and IQGAP1 KO genetic rescue in GGTase-I-deficient mice with co-IP/ubiquitination and GTP-loading assays

    PMID:31484924

    Open questions at the time
    • E3 ligase for non-prenylated Rac1 not identified
  42. 2019 High

    Demonstrated that short-lived, effector-dependent Rac1 immobilizations at the lamellipodium tip trigger WRC-dependent actin branching needed for protrusion.

    Evidence Single-particle tracking, tip-localized optogenetic activation, and Rac1 effector-loop/WRC mutants

    PMID:31422887

    Open questions at the time
    • Mechanism converting transient immobilization into sustained WRC output not fully defined
  43. 2020 Medium

    Showed PKCα selectively promotes Rac1 activation during single-spine structural plasticity via its PDZ-binding domain.

    Evidence Two-photon uncaging, single-spine FRET biosensors, PKCα shRNA, and PDZ mutant

    PMID:32019972

    Open questions at the time
    • GEF/effector linking PKCα to Rac1 not defined
    • Single lab
  44. 2020 High

    Revealed local prenylation of newly synthesized Rac1 targets it to TrkA endosomes to drive axonal receptor trafficking and target innervation.

    Evidence Conditional GGTase KO in sympathetic neurons, compartmentalized prenylation assays, and TrkA endosome imaging

    PMID:32533921

    Open questions at the time
    • Effectors mediating Rac1's endosomal trafficking role not identified
  45. 2020 High

    Showed IQGAP1 sustains VEGF-induced Rac1 activation via VEGFR2–Src to drive endothelial migration and choroidal neovascularization.

    Evidence IQGAP1 KO mice, Rac1-binding-deficient mutant, Rac1-GTP pulldown, and CNV model

    PMID:32783108

    Open questions at the time
    • How IQGAP1 binding extends GTP-loading kinetically not fully resolved
  46. 2022 Medium

    Placed Rac1 within Hedgehog signaling, where Smo–Vav2-activated Rac1 phosphorylates KIF3A, stabilizes IFT88, and enables Gli nuclear translocation.

    Evidence Smo–Vav2 co-IP, Rac1 activation, KIF3A phosphorylation, IFT88 stability, SuFu–Gli co-IP, and Rac1 conditional KO mice

    PMID:35154488

    Open questions at the time
    • Direct vs indirect Rac1 phosphorylation of KIF3A not separated
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unifying structural and quantitative model integrating Rac1's lipid-anchored nanocluster assembly, prenylation/glutathiolation switches, and the combinatorial GEF/GAP code that selects among its many effector and transcriptional outputs remains unresolved.
  • No single model reconciles spatial nanodomain control with effector selection
  • E3 ligase(s) for ubiquitin-dependent Rac1 turnover not identified across contexts
  • Determinants of nuclear vs membrane Rac1 function not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0060089 molecular transducer activity 4 GO:0008289 lipid binding 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 5 GO:0005634 nucleus 3 GO:0005856 cytoskeleton 3 GO:0005768 endosome 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-168256 Immune System 5 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 1
Partners
CALMODULINCAVEOLIN-1CYRI/FAM49IQGAP1PAK1TIAM1VAV2Β-PIX
Complex memberships
Rac1–IQGAP1–CLIP-170 complexTiam1/Rac1/RORγt nuclear complexWAVE regulatory complex (WRC/Scar)gp91phox/p67phox NADPH oxidase complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Activated Rac1 (and Cdc42) interacts with IQGAP1, and IQGAP1 in turn binds CLIP-170, forming a tripartite Rac1/Cdc42–IQGAP1–CLIP-170 complex that captures microtubule plus-ends at the cortical leading edge to polarize the microtubule array and establish cell polarity. Expression of an IQGAP1 mutant defective in Rac1/Cdc42 binding induces multiple leading edges. Co-immunoprecipitation, GFP-fusion live imaging, dominant-negative/truncation expression in Vero fibroblasts Cell High 12110184
1999 The Salmonella Typhimurium effector SptP acts as a GAP (GTPase-activating protein) directly for Rac-1 and Cdc42, stimulating GTP hydrolysis and thereby reversing the actin cytoskeletal changes (membrane ruffling) induced by bacterial invasion. In vitro GAP assay with purified SptP and Rac-1/Cdc42, cell-based phenotypic rescue Nature High 10499590
1997 Both Rac1 and Cdc42 are required for FcγR-mediated phagocytosis and for membrane ruffling in macrophages; dominant-inhibitory Rac1 N17 blocks phagocytic cup formation and particle internalization without fully blocking F-actin accumulation, indicating a role downstream of actin recruitment in membrane remodeling. Expression of dominant-negative Rac1 N17 and Cdc42 N17 in transfected RAW 264.7 macrophages; F-actin staining; phagocytosis assay The Journal of experimental medicine High 9348306
1998 Dominant-inhibitory Rac1 blocks particle internalization and prevents phagocytic cup closure during FcεRI-mediated phagocytosis in RBL-2H3 mast cells; Rac1 and CDC42 have distinct functions (Rac1-inhibited cells show thin membrane protrusions that fail to fuse, while CDC42-inhibited cells show pedestal-like structures), and inhibition of both is accompanied by persistence of phosphotyrosine around bound particles, suggesting Rac1 coordinates actin organization and membrane extension. Stable transfection of dominant-negative Rac1 and CDC42 in RBL-2H3 cells; F-actin staining; phagocytosis assay; phosphotyrosine immunofluorescence The EMBO journal High 9799231
1996 Rac1 is a required downstream component of the Vav oncogene signaling pathway that activates JNK/SAPK; co-expression of dominant-inhibitory Rac1 N17 dramatically reduces JNK/SAPK stimulation by oncogenic Vav and reduces Vav-induced focus formation in NIH3T3 cells, establishing Rac1 as an effector linking Vav (a Rho-family GEF) to the JNK/SAPK kinase cascade. Transient co-expression in COS-7 cells; JNK/SAPK kinase assay; focus-formation assay in NIH3T3 cells with dominant-negative Rac1 Oncogene Medium 8760286
1998 Rac1 C-terminus (polybasic region) is necessary and sufficient to constitutively associate with a type I PtdInsP 5-kinase and a diacylglycerol kinase (DGK) independent of GTP-loading; RhoGDI associates with this lipid kinase complex primarily via its interaction with Rac1; specific phospholipids enhance the Rac–lipid kinase interaction. In vitro binding with chimeric/truncation/peptide Rac1 constructs; co-purification by liquid chromatography; in vivo co-immunoprecipitation with RhoGDI Molecular and cellular biology High 9447972
1996 Rac1, in its GTP-bound form, directly binds alpha- and beta-tubulin via its effector domain (D38A mutation abolishes interaction); GTPase-dead mutants G12V and Q61L retain tubulin binding, indicating the interaction requires the active conformation but not GTP hydrolysis. Overlay binding assay with [γ-32P]GTP-labeled Rac1 on cell extract nitrocellulose; purification and identification of 55-kDa binding proteins as tubulin; binding assay with purified tubulin and Rac1 point mutants The Journal of biological chemistry High 8631991
2000 Membrane recruitment of activated Rac1 alone is sufficient to trigger actin polymerization and phagocytic particle internalization; the Rac1 effector-loop mutation F37L abolishes this activity, demonstrating that phagocytosis requires downstream effector binding by Rac1. Rapamycin-inducible membrane-recruitment system (FKBP–FRB bridge) for activated Rac1; actin immunofluorescence; latex bead internalization assay; cytochalasin D inhibition; site-directed mutagenesis Journal of cell science High 10934035
2003 Genetic deletion of both Rac1 and Rac2 in mice causes massive egress of hematopoietic stem/progenitor cells from bone marrow; Rac1 specifically (not Rac2) is required for HSC/P engraftment in irradiated recipients; Rac2 (not Rac1) regulates superoxide production and directed neutrophil migration, demonstrating non-redundant isoform-specific roles. Conditional gene targeting (Rac1−/−, Rac2−/−, Rac1/2 double KO) in mice; bone marrow transplantation; NADPH oxidase/superoxide assay; migration assay Science High 14564009
2005 Conditional deletion of Rac1 in adult mouse epidermis drives epidermal stem cells to divide and undergo terminal differentiation; Rac1 exerts this effect by negatively regulating c-Myc through PAK2 phosphorylation, placing Rac1 upstream of PAK2 and c-Myc in the stem cell regulatory axis. Inducible conditional Rac1 KO in mouse epidermis; histology; BrdU incorporation; immunostaining for c-Myc and PAK2; epistasis analysis Science High 16081735
2006 Rac1 is required in cardiomyocytes for NADPH oxidase activation and cardiac hypertrophy: cardiac-specific Rac1 deletion abolishes gp91(phox)–p67(phox) interaction, reduces NADPH oxidase activity and myocardial oxidative stress, and attenuates angiotensin II–induced hypertrophy in vivo. Cardiomyocyte-specific inducible Rac1 KO mice; co-immunoprecipitation of gp91(phox) and p67(phox); NADPH oxidase activity assay; ROS measurement; echocardiography Proceedings of the National Academy of Sciences of the United States of America High 16651530
2007 Rac1 signaling promotes chondrogenesis and N-cadherin expression in mesenchymal precursors; pharmacological or genetic inhibition of Rac1 reduces Sox9/Sox5/Sox6 transcription factor expression and cartilage markers, while Rac1 overexpression increases them; Rac1 and Cdc42 act through partially distinct mechanisms during chondrogenesis. Pharmacological Rac1 inhibition and dominant-active overexpression in micromass cultures and ATDC5 cells; conditional Rac1 KO primary micromass cultures; RT-PCR; immunoblot; N-cadherin staining The Journal of biological chemistry Medium 17573353
2005 Rac1 and Cdc42 promote chondrocyte hypertrophy and apoptosis through activation of the p38 MAP kinase pathway; pharmacological p38 inhibition blocks the effects of Rac1 and Cdc42 overexpression on hypertrophy and apoptosis, and Rac1/Cdc42 activity is required for maximal collagen X promoter activity, antagonizing RhoA signaling. Transient/stable transfection in primary chondrocytes and ATDC5 cells; luciferase reporter; TUNEL assay; caspase activity; phospho-p38 immunoblot; p38 inhibitor epistasis Journal of bone and mineral research Medium 15883643
2012 The centralspindlin component CYK4 functions as a GAP specifically for Rac1 (not RhoA) at the cell equator during anaphase; CYK4 GAP activity suppresses Rac1-dependent ARHGEF7 and PAK1 effector pathways required for cell adhesion, thereby spatially segregating cell adhesion from contractile ring activity during cytokinesis. In vitro GAP assay with purified CYK4; CYK4 GAP mutant expression; depletion of ARHGEF7/PAK1 rescue experiments; vinculin staining; cytokinesis phenotyping The Journal of cell biology High 22945935
2006 p66shc increases the Rac1-specific GEF activity of Sos1 by displacing Sos1 from Grb2 (via competition of the PPLP motif in the p66shc CH2 domain for the C-SH3 domain of Grb2) and promoting formation of the Sos1–Eps8–E3b1 tricomplex, resulting in Rac1 activation and oxidative stress. In vitro GEF activity assay; co-immunoprecipitation of Sos1/Grb2/Eps8/E3b1; domain-mapping with CH2 mutants; Rac1 activation assay (GST-PBD pulldown) The Journal of cell biology High 16520382
2010 Rac1 binds the adaptor protein caveolin-1 (Cav1); Rac1 activity promotes Cav1 accumulation at peripheral adhesions; Cav1 controls Rac1 protein levels by regulating ubiquitylation and proteasomal degradation of activated (GTP-bound) Rac1 in an adhesion-dependent manner, providing a non-canonical mechanism to terminate Rac1 signaling. Co-immunoprecipitation; Cav1-KO fibroblasts; siRNA/shRNA depletion; ubiquitylation assay; effector-binding assay with ubiquitylation-deficient Rac1 mutant Journal of cell science High 20460433
2017 Rac1 partitions into nanoclusters of 50–100 molecules at the plasma membrane through interaction of its polybasic tail with PIP2 and PIP3; additional interactions with GEFs, GAPs, and effectors enrich nanoclusters in protruding regions, generating spatial gradients of Rac1 signaling nanodomains. Single-molecule imaging (SPT); super-resolution microscopy (PALM/STORM); pharmacological lipid perturbation Cell reports Medium 29141223
2018 Cdc42 and Rac1 gradients during cell migration are set by spatial patterns of GEFs and GAPs, not by transport; Rac1 gradient shaping specifically requires the GAP β2-chimaerin, which is localized to the cell tip through feedbacks from both Cdc42 and Rac1; the spatial extent of the Rac1 gradient controls cell migration speed. Optogenetics (light-controlled GEF recruitment); micropatterning; FRET biosensor imaging; β2-chimaerin KO/depletion Nature communications High 30446664
2007 Rac1 and Cdc42 use partially overlapping but distinct binding interfaces on IQGAP1: switch II residues Asp-63, Arg-68, and Leu-70 are critical for Rac1–IQGAP1 binding but not for Cdc42–IQGAP1 binding; residues 32 and 36 in switch I affect both; the Rho insert loop does not contribute; IQGAP1 and RhoGAP binding sites on Rac1 overlap only partially. Site-directed mutagenesis of Rac1 and Cdc42; binding affinity measurements (ITC/fluorescence); competition assays The Journal of biological chemistry High 17984089
2005 Yersinia pseudotuberculosis YopE RhoGAP inactivates the membrane-associated pool of Rac1 globally, while YopT protease removes Rac1's membrane-targeting motif, releasing activated Rac1 into the cytoplasm/nucleus where it interacts with nuclear GEFs; the two effectors compete for membrane-associated Rac1, producing two spatially distinct pools with different activation states. FRET-based Rac1 activation biosensor imaging in living cells; bacterial infection with YopE and YopT mutant strains PLoS pathogens Medium 16228016
2004 DGKγ (diacylglycerol kinase gamma) acts as an upstream suppressor of Rac1 via its catalytic activity; kinase-dead DGKγ (dominant-negative) selectively activates Rac1 (not Cdc42) and induces lamellipodia, while constitutively active DGKγ suppresses PDGF-induced lamellipodia; endogenous DGKγ co-immunoprecipitates with Rac1; dominant-negative Rac1 blocks lamellipodia induced by kinase-dead DGKγ, placing DGKγ upstream of Rac1. Expression of kinase-dead and constitutively active DGKγ mutants; co-immunoprecipitation; dominant-negative Rac1 epistasis; Rac1 activation assay (GST-PBD pulldown); confocal co-localization The Journal of biological chemistry Medium 15102830
2011 S6K1 acts upstream of Rac1 during platelet activation on fibrinogen; S6K1 and Rac1 interact in a protein complex with the Rac1 GEF TIAM1 and co-localize with actin at the platelet lamellipodial edge; mTOR inhibitors block Rac1 activation and platelet spreading without affecting Src or FAK, placing mTOR–S6K1 upstream of Rac1 in this pathway. Co-immunoprecipitation (S6K1–Rac1–TIAM1 complex); pharmacological inhibition of S6K1, mTOR, Src, FAK; Rac1 activation assay; platelet spreading assay under shear flow Blood Medium 21757621
2006 DOCK2 associates with CrkL (via two separate DOCK2 regions binding the CrkL SH3 domain) in hematopoietic cells; a DOCK2-dCS mutant that cannot bind CrkL significantly inhibits CrkL-induced Rac1 activation; DOCK2 also associates with the Rac1 GEF Vav in Jurkat cells, placing DOCK2 in a CrkL–DOCK2–Vav complex upstream of Rac1. Co-immunoprecipitation (in vivo and in vitro); GST pulldown; Rac1 activation assay; immunocytochemistry Blood Medium 12393632
2012 Rac1 forms a nuclear complex with the GEF Tiam1 and the transcription factor RORγt in Th17 cells; this complex binds and activates the Il17a promoter; deletion of Rac1 in T cells more potently reduces IL-17A expression and EAE than Tiam1 deficiency alone. Co-immunoprecipitation of Tiam1/Rac1/RORγt complex; ChIP at the Il17 promoter; T-cell-specific Rac1 KO mice; EAE model; pharmacological Rac1 inhibition Nature communications High 27725632
2012 Schwann cell myelination requires Rac1; Rac1 KO abrogates PAK phosphorylation and reduces NF2/merlin phosphorylation; NF2/merlin mutation rescues myelin deficits in Rac1-CKO mice; cAMP levels are reduced in Rac1-CKO SCs and elevation of cAMP restores myelination, placing NF2/merlin and cAMP downstream of Rac1 in a myelination pathway. Conditional Rac1 KO in Schwann cells; immunoblot for phospho-PAK and phospho-merlin; genetic rescue with NF2/merlin mutant in vivo; rolipram (cAMP elevation) pharmacological rescue in vivo The Journal of neuroscience High 23197717
2001 Constitutively active Rac1-V12 inhibits anoikis (suspension-induced apoptosis) in MDCK epithelial cells by reducing caspase activity and DNA fragmentation; Rac1-mediated survival depends on PI3K activity; ERK, p38, and NF-κB pathways are activated by Rac1-V12 but are largely dispensable for the survival effect. Expression of Rac1-V12 in MDCK cells in suspension; caspase assay; DNA fragmentation; pharmacological inhibition of PI3K, ERK, p38, NF-κB The Journal of biological chemistry Medium 11369774
2009 CCK activates Rac1 in pancreatic acini through Gα13 and Gαq acting cooperatively (but not Gαs or Gαi); RGS-2 (Gαq inhibitor) and p115-RGS (Gα12/13 inhibitor) both abolish CCK-induced Rac1 activation via a PLC-independent pathway; RhoA is activated exclusively through Gα13. Active Gα expression constructs; Rac1/RhoA activation assays (pulldown); RGS domain inhibitors; RT-PCR and western for Gα13 American journal of physiology. Cell physiology Medium 19940064
2008 NOD2 stimulation activates Rac1 in human monocytes; β-PIX co-immunoprecipitates with NOD2 and Rac1 upon MDP stimulation; knockdown of β-PIX or Rac1 abrogates membrane recruitment of NOD2 and NOD2 interaction with its negative regulator Erbin, demonstrating that β-PIX–Rac1 mediate NOD2 trafficking and negative feedback regulation. Rac1 activation assay; co-immunoprecipitation of NOD2–β-PIX–Rac1; siRNA knockdown; immunofluorescence for NOD2 membrane localization; IL-8/NF-κB reporter Journal of immunology Medium 18684957
2006 Integrin-linked kinase (ILK) activates Rac1 via β-PIX; ILK associates with PKL and the Rac1/Cdc42 GEF β-PIX; dominant-negative β-PIX reverses ILK-induced Rac1 activation; ILK knockdown reduces active Rac1 levels, placing β-PIX downstream of ILK and upstream of Rac1 in integrin-mediated cell spreading. Co-immunoprecipitation of ILK–PKL–β-PIX; Rac1 activation assay (GST-PBD pulldown); siRNA knockdown; dominant-negative β-PIX epistasis; ILK-GFP-F overexpression FASEB journal Medium 16723384
2013 GluN3A-containing NMDA receptors bind GIT1, limiting GIT1 synaptic localization and its ability to complex β-PIX, thereby decreasing Rac1 activation and PAK phosphorylation in spines and reducing spine density/size; knockdown of GluN3A increases GIT1/β-PIX complex formation and Rac1/PAK activation. GluN3A–GIT1 binding is regulated by synaptic activity. Co-immunoprecipitation of GluN3A–GIT1; Rac1 activation assay; GluN3A KO mice; shRNA knockdown; immunofluorescence; PAK phosphorylation immunoblot Proceedings of the National Academy of Sciences of the United States of America High 24297929
2014 Rac1 contains a redox-sensitive cysteine (Cys18) with a lowered pKa; oxidation of Cys18 by glutathione (glutathiolation) greatly perturbs guanine nucleotide binding and promotes nucleotide exchange, activating Rac1; Rac1 is glutathiolated in primary chondrocytes; the C18D mimetic mutant shows enhanced GTP-loading and promotes lamellipodia formation in cells. Mass spectrometry identification of glutathiolation; in vitro nucleotide-exchange assay with oxidized Rac1; pKa measurement; C18D/C18S mutagenesis; GTP-bound Rac1 pulldown in cells; lamellipodia formation assay Free radical biology & medicine High 25289457
2006 Alsin, a GEF for Rac1 (and Rab5), supports motoneuron survival and axon growth through Rac1 signaling; alsin knockdown–induced cell death and reduced axon growth are mimicked by dominant-negative Rac1 and fully rescued by constitutively active Rac1, while dominant-negative/active Rab5 has no such effect. siRNA knockdown of alsin in embryonic rat spinal motoneurons; expression of dominant-negative and constitutively active Rac1 and Rab5; cell survival counting; axon length measurement Annals of neurology Medium 16802292
2006 Loss or gain of Rac1 activity induces premature senescence in primary MEFs through increased reactive oxygen species (ROS) production and p53 activation (phospho-Ser15); ROS inhibitor blocks DNA damage foci formation; genetic p53 deletion reverses senescence in both Rac1−/− and L61Rac1 cells, placing ROS-mediated genomic instability and p53 upstream of Rac1-regulated senescence. Rac1 gene-targeted MEFs; constitutively active L61Rac1; ROS measurement; TUNEL; phospho-H2AX foci; p53 phosphorylation; p53 genetic deletion epistasis The Journal of biological chemistry Medium 17032649
2019 Non-prenylated Rac1 has high affinity for IQGAP1, which facilitates both GTP exchange and ubiquitination-mediated degradation of Rac1; inactivating IQGAP1 normalizes Rac1 GTP-loading and reduces inflammation; heterozygous Rac1 deletion (but not Rhoa or Cdc42) reverses arthritis in GGTase-I-deficient mice. Prenylation of Rac1 by GGTase-I therefore normally restrains Rac1 effector interactions. Rac1+/− genetic rescue in GGTase-I KO mice; IQGAP1 KO mice; co-immunoprecipitation and ubiquitination assays; Rac1 GTP-loading assay; inflammatory phenotype scoring Nature communications High 31484924
2018 CYRI (Fam49) binds activated Rac1 via its DUF1394 domain, locally suppresses Scar/WAVE recruitment at the cell edge, limits protrusion size and duration, and thereby regulates pseudopod polarity, chemotaxis, and epithelial polarization; CYRI-depleted cells show larger, longer-lived optogenetically induced pseudopods. Co-immunoprecipitation and biochemical binding assay (DUF1394–Rac1); CYRI KO/overexpression; optogenetic Rac1 activation; Scar/WAVE immunofluorescence; migration/chemotaxis assays Nature cell biology High 30054448
2019 Transient immobilizations of activated Rac1 at the lamellipodium tip correlate with its activation and depend on effector binding including the WAVE regulatory complex (WRC); optogenetic Rac1 activation close to the lamellipodium tip (but not behind it) is required for efficient membrane protrusion; these data establish that short-lived Rac1 activation triggers WRC-dependent actin branching at the lamellipodium tip. Single-particle tracking (SPT); optogenetic Rac1 activation (Tiam1 membrane recruitment); Rac1 effector-loop mutants; WRC mutant cells; super-resolution imaging Current biology High 31422887
2009 Activated Rac1 (Rac(V12)) induces upregulation of IL-6 family cytokines, which activate gp130/Stat3 signaling; gp130 knockdown reduces Stat3 activity, cell migration, and proliferation induced by Rac(V12), identifying gp130/Stat3 as an essential effector pathway downstream of activated Rac1. Expression of Rac1(V12) in HC11 cells; gp130 siRNA knockdown; Stat3 luciferase reporter; IL-6 mRNA quantification; cell migration/proliferation assays Experimental cell research Medium 19852956
2009 Rac1 signaling inhibits the transcriptional repressor BCL-6; active Rac1 mutants cause BCL-6 to lose nuclear dot localization and become non-chromatin-bound, inducing expression of BCL-6 target genes NF-κB1/p105 and CD44; PAK1 mediates this inhibition downstream of Rac1 and can directly phosphorylate BCL-6; notably, the splice variant Rac1b does not stimulate these effects. Active Rac1 mutant transfection; NSC23766 pharmacological inhibition; luciferase reporter; fractionation/immunofluorescence for BCL-6; in vitro PAK1 kinase assay with BCL-6 substrate Molecular and cellular biology Medium 19487462
2011 Rac1 is sequentially activated downstream of Rap1/CalDAG-GEFI via GPVI in platelets; Rac1 in turn provides positive feedback for both CalDAG-GEFI- and P2Y12-dependent Rap1 activation via calcium mobilization and granule/ADP release; Rac1 controls lamellipodia formation, clot retraction, and granule release; two pools of Rac1 exist, one directly downstream of GPVI and one downstream of Rap1. Rac1 inhibitor EHT 1864 in platelets; CalDAG-GEFI/P2Y12 double KO mice; Rac1 activation assay; platelet spreading; calcium flux; clot retraction assay Arteriosclerosis, thrombosis, and vascular biology Medium 22075250
2012 Wnt3a stimulation activates Rac1 by promoting CK1-dependent phosphorylation of p120-catenin, enabling its release from E-cadherin and binding to the Rac1 GEF Vav2 and Rac1 itself; this trimeric p120-catenin/Vav2/Rac1 complex facilitates Rac1 activation; p120-catenin mutants defective in E-cadherin release or Vav2/Rac1 binding cannot rescue p120-catenin depletion in Xenopus gastrulation. Co-immunoprecipitation of p120-catenin/Vav2/Rac1; Rac1 activation assay; Src/Fyn and CK1 phosphorylation; Xenopus depletion/rescue assays Journal of cell science Medium 22946057
2020 PKCα positively regulates Rac1 activation during single-spine structural plasticity in neurons; removal of PKCα from the postsynapse attenuates Rac1 (but not Ras or Cdc42) activation; disruption of PKCα's PDZ binding domain impairs both Rac1 activation and structural spine remodeling. Two-photon uncaging; FRET biosensors for Rac1, Cdc42, Ras in single spines; PKCα shRNA knockdown; PDZ-domain PKCα mutant Scientific reports Medium 32019972
2020 NGF triggers prenylation (geranylgeranylation) of newly synthesized Rac1 in sympathetic axons in a local protein-synthesis-dependent manner; newly prenylated Rac1 localizes to TrkA-harboring endosomes in axons and promotes receptor trafficking necessary for axon growth; conditional KO of prenylation machinery abolishes sympathetic axon target innervation. Conditional KO of geranylgeranyltransferase in sympathetic neurons; axonal compartment isolation; prenylation assay in isolated axons; TrkA endosome co-localization; axon growth assays Developmental cell High 32533921
1994 Expression of α1-chimaerin (a Rac1-specific GAP) in NIH3T3 fibroblasts reduces Rac1 activity (confirmed by in-extract GAP assay) and impairs actin stress fiber formation, focal adhesion assembly (vinculin clusters), and integrin-mediated adhesion to fibronectin following growth factor stimulation, establishing that GAP-mediated inactivation of Rac1 negatively regulates actin cytoskeletal organization. Stable transfection of α1-chimaerin; in-extract Rac1 GAP activity assay (regulated by phosphatidylserine/phorbol ester); actin/vinculin immunofluorescence; fibronectin adhesion assay Journal of cellular biochemistry Medium 7534315
2011 Rac1 and calmodulin (CaM) interact with high binding affinity through the Rac1 polybasic region and its prenyl group; CaM inhibition inactivates Rac1, increases Rac1–PIP5K interaction, and induces extensive PI4,5P2-positive tubular plasma-membrane invaginations via an ARF6-dependent clathrin-independent endocytic pathway; inactive Rac1 mutant expression enhances tubulation by recruiting PIP5K, while active Rac1 impairs it. Binding affinity measurements (Rac1–CaM); CaM inhibitor treatment; constitutively active/inactive Rac1 mutant expression; PI4,5P2 immunofluorescence; endocytosis assays Traffic Medium 21883766
2020 IQGAP1 mediates sustained VEGF-induced Rac1 activation in choroidal endothelial cells via VEGFR2–Src–Rac1 signaling; IQGAP1 binding to Rac1-GTP sustains Rac1 activation; an IQGAP1 construct unable to bind Rac1 abolishes sustained Rac1 activation; Iqgap1−/− mice have reduced Rac1-GTP and choroidal neovascularization. IQGAP1 KO mice; IQGAP1-Rac1 binding-deficient mutant; Rac1-GTP pulldown; Src/VEGFR2 inhibition; CEC migration and tube formation assays; laser-induced CNV model Angiogenesis High 32783108
2022 Smo activation by Hh ligand leads to Smo binding Vav2, increased Vav2 phosphorylation at Y172, and consequent Rac1 activation; active Rac1 then phosphorylates KIF3A at S689/T694, stabilizes IFT88, and dampens SuFu–Gli complex formation, enabling Gli nuclear translocation and Hh target gene expression; Rac1 deficiency in mouse limb bud ectoderm impedes Gli nuclear translocation. Co-immunoprecipitation of Smo–Vav2; Vav2 phosphorylation assay; Rac1 activation assay; KIF3A phosphorylation; IFT88 stability; SuFu–Gli co-IP; Rac1 conditional KO mouse; human MB tissue analysis Theranostics Medium 35154488
2018 Thrombospondin–α2δ-1 interaction promotes synaptogenesis postsynaptically via Rac1; postsynaptic (but not presynaptic) α2δ-1 is required and sufficient for TSP-induced synaptogenesis and spine formation in vivo; an autism-linked α2δ-1 mutant cannot rescue these defects. Cell-type-specific KO of α2δ-1; TSP-induced synaptogenesis assay; Rac1 activation assay; electron microscopy; in vivo spine counting The Journal of cell biology Medium 30054448

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell 503 12110184
1999 A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature 431 10499590
2003 Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science (New York, N.Y.) 398 14564009
1997 Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes. The Journal of experimental medicine 343 9348306
2009 Rac1 GTPase: a "Rac" of all trades. Cellular and molecular life sciences : CMLS 297 19151919
2006 Requirement of Rac1 in the development of cardiac hypertrophy. Proceedings of the National Academy of Sciences of the United States of America 240 16651530
2005 Stem cell depletion through epidermal deletion of Rac1. Science (New York, N.Y.) 216 16081735
1998 Fc receptor-mediated phagocytosis requires CDC42 and Rac1. The EMBO journal 199 9799231
2006 Rac1 and Rac2 regulate macrophage morphology but are not essential for migration. Journal of cell science 156 16772332
1996 Rac-1 dependent stimulation of the JNK/SAPK signaling pathway by Vav. Oncogene 154 8760286
1998 Characterization of a Rac1- and RhoGDI-associated lipid kinase signaling complex. Molecular and cellular biology 135 9447972
2018 Thrombospondin receptor α2δ-1 promotes synaptogenesis and spinogenesis via postsynaptic Rac1. The Journal of cell biology 125 30054448
2000 Membrane recruitment of Rac1 triggers phagocytosis. Journal of cell science 121 10934035
2011 S6K1 and mTOR regulate Rac1-driven platelet activation and aggregation. Blood 112 21757621
1996 The Ras-related GTPase Rac1 binds tubulin. The Journal of biological chemistry 112 8631991
2007 Rac1 signaling stimulates N-cadherin expression, mesenchymal condensation, and chondrogenesis. The Journal of biological chemistry 104 17573353
2021 Rac1, A Potential Target for Tumor Therapy. Frontiers in oncology 98 34079763
2012 CYK4 inhibits Rac1-dependent PAK1 and ARHGEF7 effector pathways during cytokinesis. The Journal of cell biology 90 22945935
2005 Rac1/Cdc42 and RhoA GTPases antagonistically regulate chondrocyte proliferation, hypertrophy, and apoptosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 90 15883643
2009 Role of Rac 1 and cAMP in endothelial barrier stabilization and thrombin-induced barrier breakdown. Journal of cellular physiology 88 19472214
2016 Rac1 and RhoA: Networks, loops and bistability. Small GTPases 87 27533896
2016 Impact of point mutation P29S in RAC1 on tumorigenesis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 82 27699663
2021 KDM6A-ARHGDIB axis blocks metastasis of bladder cancer by inhibiting Rac1. Molecular cancer 78 34006303
2006 Sos-mediated activation of rac1 by p66shc. The Journal of cell biology 78 16520382
2010 Focal-adhesion targeting links caveolin-1 to a Rac1-degradation pathway. Journal of cell science 77 20460433
2017 Gradients of Rac1 Nanoclusters Support Spatial Patterns of Rac1 Signaling. Cell reports 76 29141223
2013 Activation of Rac-1 and RhoA contributes to podocyte injury in chronic kidney disease. PloS one 73 24244677
2018 Compartmentalisation of RAC1 signalling. Current opinion in cell biology 71 29723737
2019 Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions. Nature communications 70 31484924
2018 Fam49/CYRI interacts with Rac1 and locally suppresses protrusions. Nature cell biology 70 30250061
2020 Sarcoidosis and the mTOR, Rac1, and Autophagy Triad. Trends in immunology 69 32122794
2001 Rac1 protects epithelial cells against anoikis. The Journal of biological chemistry 69 11369774
2020 Rac1 Signaling: From Intestinal Homeostasis to Colorectal Cancer Metastasis. Cancers 68 32178475
2015 Modulation of actin dynamics by Rac1 to target cognitive function. Journal of neurochemistry 63 25818528
2015 RAC1 P29S regulates PD-L1 expression in melanoma. Pigment cell & melanoma research 63 26176707
2011 Rap1-Rac1 circuits potentiate platelet activation. Arteriosclerosis, thrombosis, and vascular biology 63 22075250
2005 Activation of Rac-1 and Cdc42 stabilizes the microvascular endothelial barrier. Histochemistry and cell biology 63 16195887
2002 DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines. Blood 63 12393632
2018 Optogenetic dissection of Rac1 and Cdc42 gradient shaping. Nature communications 62 30446664
2005 Selective Rac-1 inhibition protects from diabetes-induced vascular injury. Circulation research 61 16357302
2006 Alsin/Rac1 signaling controls survival and growth of spinal motoneurons. Annals of neurology 59 16802292
2016 Rab7a regulates cell migration through Rac1 and vimentin. Biochimica et biophysica acta. Molecular cell research 58 27888097
2006 Rac1 and Cdc42 have different roles in Candida albicans development. Eukaryotic cell 57 16467473
2012 Rac1 controls Schwann cell myelination through cAMP and NF2/merlin. The Journal of neuroscience : the official journal of the Society for Neuroscience 56 23197717
2007 The IQGAP1-Rac1 and IQGAP1-Cdc42 interactions: interfaces differ between the complexes. The Journal of biological chemistry 56 17984089
2005 Yersinia pseudotuberculosis spatially controls activation and misregulation of host cell Rac1. PLoS pathogens 56 16228016
2008 Beta-PIX and Rac1 GTPase mediate trafficking and negative regulation of NOD2. Journal of immunology (Baltimore, Md. : 1950) 55 18684957
2020 RAC1 as a Therapeutic Target in Malignant Melanoma. Trends in cancer 54 32460002
2004 Regulation of anoikis by Cdc42 and Rac1. Experimental cell research 54 15093747
2004 Diacylglycerol kinase gamma serves as an upstream suppressor of Rac1 and lamellipodium formation. The Journal of biological chemistry 54 15102830
2018 Post-Translational Modification and Subcellular Distribution of Rac1: An Update. Cells 53 30544910
2016 GEFs: Dual regulation of Rac1 signaling. Small GTPases 53 27314616
2014 mTOR regulate EMT through RhoA and Rac1 pathway in prostate cancer. Molecular carcinogenesis 50 25043657
2014 Rac-1 as a new therapeutic target in cerebro- and cardio-vascular diseases. Current drug targets 49 25345393
2019 Transient Activations of Rac1 at the Lamellipodium Tip Trigger Membrane Protrusion. Current biology : CB 48 31422887
2006 Rac1 GTPase regulates cell genomic stability and senescence. The Journal of biological chemistry 48 17032649
2016 Tiam1/Rac1 complex controls Il17a transcription and autoimmunity. Nature communications 47 27725632
2017 Suppression of RAC1-driven malignant melanoma by group A PAK inhibitors. Oncogene 45 29059171
2009 Rac1 regulates pancreatic islet morphogenesis. BMC developmental biology 45 19126201
2022 Rac1 as a therapeutic anticancer target: Promises and limitations. Biochemical pharmacology 43 35853497
2006 Regulation of cell-matrix adhesion dynamics and Rac-1 by integrin linked kinase. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 43 16723384
2015 Distinct predictive performance of Rac1 and Cdc42 in cell migration. Scientific reports 40 26634649
2006 NADPH oxidase subunits (NOX-1, p22phox, Rac-1) and tacrolimus-induced nephrotoxicity in a rat renal transplant model. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 38 17085464
2014 Rac1 signaling is critical to cardiomyocyte polarity and embryonic heart development. Journal of the American Heart Association 37 25315346
2014 RAC1 and melanoma. Clinical therapeutics 37 25465943
2016 Emerging roles of RAC1 in treating lung cancer patients. Clinical genetics 36 27790713
2013 GluN3A expression restricts spine maturation via inhibition of GIT1/Rac1 signaling. Proceedings of the National Academy of Sciences of the United States of America 36 24297929
2022 Overexpressed or hyperactivated Rac1 as a target to treat hepatocellular carcinoma. Pharmacological research 35 35405309
2014 CDC-42 and RAC-1 regulate opposite chemotropisms in Neurospora crassa. Journal of cell science 34 24790223
2012 Upon Wnt stimulation, Rac1 activation requires Rac1 and Vav2 binding to p120-catenin. Journal of cell science 34 22946057
2002 Opsonization modulates Rac-1 activation during cell entry by Leishmania amazonensis. Infection and immunity 34 12117970
2014 Redox regulation of Rac1 by thiol oxidation. Free radical biology & medicine 33 25289457
2013 Expression and significance of Rac1, Pak1 and Rock1 in gastric carcinoma. Asia-Pacific journal of clinical oncology 32 23298303
2012 Association of syntenin-1 with M-RIP polarizes Rac-1 activation during chemotaxis and immune interactions. Journal of cell science 32 22349701
2004 Overexpression of Rac-1 small GTPase binding protein in oral squamous cell carcinoma. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 32 15170282
2009 Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration. Experimental cell research 30 19852956
2020 Rac1 is a downstream effector of PKCα in structural synaptic plasticity. Scientific reports 29 32019972
2005 Regulation of p21-activated kinase-independent Rac1 signal transduction by nischarin. The Journal of biological chemistry 28 16002401
2020 IQGAP1 causes choroidal neovascularization by sustaining VEGFR2-mediated Rac1 activation. Angiogenesis 27 32783108
2024 Implication of Rac1 GTPase in molecular and cellular mitochondrial functions. Life sciences 26 38387701
2011 Rac1 and calmodulin interactions modulate dynamics of ARF6-dependent endocytosis. Traffic (Copenhagen, Denmark) 26 21883766
2009 CCK activates RhoA and Rac1 differentially through Galpha13 and Galphaq in mouse pancreatic acini. American journal of physiology. Cell physiology 26 19940064
2020 Prenylation of Axonally Translated Rac1 Controls NGF-Dependent Axon Growth. Developmental cell 25 32533921
2015 Rac1 Regulates Endometrial Secretory Function to Control Placental Development. PLoS genetics 25 26305333
2021 Mechanistic Differences of Activation of Rac1P29S and Rac1A159V. The journal of physical chemistry. B 24 33848152
2020 Stress-Sensitive Protein Rac1 and Its Involvement in Neurodevelopmental Disorders. Neural plasticity 24 33299404
2009 Rac1 signaling modulates BCL-6-mediated repression of gene transcription. Molecular and cellular biology 24 19487462
2022 Hedgehog signaling is controlled by Rac1 activity. Theranostics 23 35154488
2018 Verbascoside Attenuates Rac-1 and HIF-1α Signaling Cascade in Colorectal Cancer Cells. Anti-cancer agents in medicinal chemistry 23 29886834
2017 Discovery and characterization of small molecule Rac1 inhibitors. Oncotarget 23 28410221
2020 TNFAIP8L2/TIPE2 impairs autolysosome reformation via modulating the RAC1-MTORC1 axis. Autophagy 22 32460619
2019 Rac1 Activity Is Modulated by Huntingtin and Dysregulated in Models of Huntington's Disease. Journal of Huntington's disease 22 30594931
2023 Force-Loaded Cementocytes Regulate Osteoclastogenesis via S1P/S1PR1/Rac1 Axis. Journal of dental research 21 37735908
2021 Rac1 activation can generate untemplated, lamellar membrane ruffles. BMC biology 21 33849538
2020 mTORC2/Rac1 Pathway Predisposes Cancer Aggressiveness in IDH1-Mutated Glioma. Cancers 21 32224866
2017 New model for the interaction of IQGAP1 with CDC42 and RAC1. Small GTPases 21 28622072
2020 Rho A and Rac1: Antagonists moving forward. Tissue & cell 20 32746999
2015 The Ins and Outs of Small GTPase Rac1 in the Vasculature. The Journal of pharmacology and experimental therapeutics 20 26036474
2014 Elmo1 helps dock180 to regulate Rac1 activity and cell migration of ovarian cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 20 24819662
1994 Expression of alpha 1-chimaerin (rac-1 GAP) alters the cytoskeletal and adhesive properties of fibroblasts. Journal of cellular biochemistry 19 7534315

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