Affinage

RHOG

Rho-related GTP-binding protein RhoG · UniProt P84095

Length
191 aa
Mass
21.3 kDa
Annotated
2026-04-28
80 papers in source corpus 50 papers cited in narrative 50 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RhoG is a Rho-family small GTPase that functions as a critical upstream activator of Rac1, orchestrating cytoskeletal remodeling, cell migration, phagocytosis, and vesicular trafficking across diverse cell types. Activated by multiple GEFs including Trio, SGEF, Ephexin4, PLEKHG6, P-Rex1, Vav family members, and Kalirin, GTP-loaded RhoG binds ELMO proteins via their ARM repeats and recruits Dock-family GEFs (Dock180, Dock2, Dock3, Dock4, Dock5) to drive Rac1 activation at the plasma membrane — a mechanism structurally explained by cryo-EM showing that RhoG binding to ELMO1 and DOCK5 converts the complex from an autoinhibited closed conformation to an active open state (PMID:12879077, PMID:15620647, PMID:38857861). Independently of the ELMO–Dock–Rac1 axis, RhoG engages kinectin to promote microtubule-dependent vesicular transport, interacts with PI3K p85α to activate Akt-mediated survival signaling, binds Munc13-4 to enable cytotoxic granule exocytosis, and regulates focal adhesion disassembly (PMID:11689693, PMID:17570359, PMID:33513601, PMID:30914742). Biallelic loss-of-function mutations in RHOG cause defective cytotoxic lymphocyte degranulation in humans, establishing RhoG as essential for immune cytotoxicity (PMID:33513601).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    The first mechanistic question was how RhoG produces its cytoskeletal effects (ruffles, lamellipodia, filopodia): epistasis experiments showed these effects require endogenous Rac1 and Cdc42 and depend on microtubules, establishing RhoG as an upstream regulator rather than a direct effector-engaging GTPase like Rac1.

    Evidence Dominant-negative epistasis and nocodazole treatment in fibroblasts

    PMID:9614181

    Open questions at the time
    • The molecular link between RhoG and Rac1/Cdc42 activation was unknown
    • Why microtubule dependence was required was unexplained
    • Direct effectors of RhoG were not identified
  2. 2000 High

    Identifying the first GEF for RhoG, Trio's N-terminal DH domain (GEFD1/TrioD1) was shown to preferentially catalyze nucleotide exchange on RhoG over Rac1, placing Trio upstream of RhoG in a signaling cascade controlling cytoskeletal rearrangements, with structural specificity later resolved by crystallography showing residues 54 and 69 of RhoG determine GEF selectivity.

    Evidence In vitro nucleotide exchange assay, dominant-negative epistasis in fibroblasts, X-ray crystallography of TrioN DH/PH domain at 1.7 Å

    PMID:10652265 PMID:11146652 PMID:15199069

    Open questions at the time
    • Other GEFs for RhoG had not yet been identified
    • Whether Trio–RhoG signaling operates in vivo remained to be shown
  3. 2001 High

    The search for direct RhoG effectors identified kinectin as a GTP-dependent binding partner, linking RhoG to microtubule-based motor transport via the kinectin–kinesin complex and explaining the earlier observation of microtubule dependence.

    Evidence Yeast two-hybrid, co-precipitation, anti-kinectin antibody microinjection blocking RhoG morphogenic activity, time-lapse imaging of lysosomal transport

    PMID:11689693

    Open questions at the time
    • Whether kinectin mediates RhoG's effects on Rac1 activation was unclear
    • The kinectin-binding site on RhoG was not mapped
  4. 2002 High

    Multiple studies expanded the RhoG signaling network: Kalirin GEF1 was shown to activate RhoG for axon sprouting, Trio–RhoG drove neurite outgrowth in PC12 cells downstream of NGF, Vav2 and Dbs were identified as additional GEFs, and RhoG was found to engage PI3K to activate Akt-dependent survival signaling independently of Rac1.

    Evidence In vitro GEF assays, dominant-negative/active epistasis in neurons, PI3K Co-IP with constitutively active RhoG, Akt phosphorylation and UV apoptosis assays

    PMID:11803464 PMID:11864571 PMID:12177196 PMID:12376551

    Open questions at the time
    • Whether RhoG–PI3K interaction is direct or mediated by an adaptor was debated
    • The complete RhoG effector repertoire was not defined
  5. 2003 High

    The central mechanistic question — how RhoG activates Rac1 — was answered: GTP-bound RhoG directly binds ELMO, which scaffolds Dock180 into a ternary complex that functions as a Rac1 GEF, establishing the RhoG→ELMO→Dock180→Rac1 signaling cascade.

    Evidence Co-IP, pulldown, dominant-negative rescue, RNAi knockdown, in vitro GEF assay in multiple cell types

    PMID:12879077

    Open questions at the time
    • How RhoG binding alters the conformation of the ELMO–Dock complex was unknown
    • Whether other Dock family members participate was not addressed
  6. 2004 High

    The RhoG–ELMO–Dock180 module was demonstrated to operate in phagocytic engulfment of apoptotic cells (conserved in C. elegans MIG-2/CED-12), and SGEF was identified as a second RhoG-specific GEF controlling macropinocytosis.

    Evidence C. elegans genetic epistasis with loss-of-function alleles; in vitro GEF assay with GTPase specificity panel; dextran uptake and SEM in fibroblasts

    PMID:15133129 PMID:15620647

    Open questions at the time
    • How SGEF is recruited to the membrane was not defined
    • Structural basis for SGEF selectivity for RhoG was lacking
  7. 2006 High

    RhoG knockout mice revealed that RhoG is required for GPCR-stimulated neutrophil NADPH oxidase activity and early Rac1/Rac2 activation, providing the first in vivo genetic evidence for the GTPase cascade; separately, Dock4 was shown to function like Dock180 in the RhoG–ELMO module.

    Evidence RhoG−/− knockout mouse neutrophils, Rac1/Rac2 pull-down, NADPH oxidase assay; Dock4–ELMO Co-IP and translocation imaging

    PMID:16621998 PMID:17027967

    Open questions at the time
    • The specific GEF activating RhoG in neutrophils was not identified at this point
    • In vivo roles beyond innate immunity were unexplored
  8. 2007 High

    SGEF was linked to endothelial ICAM1 signaling: ICAM1 engagement recruits SGEF via its SH3 domain to activate RhoG, which is required for endothelial cup formation and leukocyte transendothelial migration, establishing RhoG in adaptive immunity and vascular biology.

    Evidence siRNA of RhoG and SGEF, rescue, Co-IP of ICAM1–SGEF, FRET-based RhoG activation, leukocyte TEM assay

    PMID:17875742

    Open questions at the time
    • Whether RhoG's role in TEM involves ELMO–Dock or direct effectors was not dissected
    • Downstream effectors at the endothelial cup were not identified
  9. 2009 High

    Upstream regulation of RhoG was clarified: a syndecan-4–synectin–RhoGDI1 complex sequesters RhoG in its inactive state, and PKCα-mediated phosphorylation of RhoGDI1 at Ser96 releases RhoG for activation; in parallel, RhoG knockout mice demonstrated its requirement for integrin endocytosis and dermal wound healing.

    Evidence Co-IP of ternary complex, RhoGDI1 S96 mutagenesis, FRET Rac1 biosensor; RhoG−/− knockout mice with wound healing and integrin endocytosis assays

    PMID:19581409 PMID:21982645

    Open questions at the time
    • Which GEF acts on RhoG after release from RhoGDI1 was not determined
    • Whether syndecan-4 regulation of RhoG occurs in non-endothelial contexts was not tested
  10. 2009 High

    Bacterial pathogenesis studies revealed that Yersinia invasin co-opts RhoG at the entry site via integrin engagement, while the type III effector YopE acts as a GAP for RhoG, directly demonstrating spatiotemporal control of RhoG activity during infection.

    Evidence FRET-based RhoG biosensor at infection sites, siRNA knockdown, bacterial internalization assays for Y. enterocolitica and Y. pseudotuberculosis

    PMID:19208761 PMID:19720752

    Open questions at the time
    • Whether other pathogens exploit RhoG was unknown
    • The precise integrin species that activates RhoG at the invasion site was not specified
  11. 2011 High

    RhoG was established as a universal phagocytosis regulator: it is uniquely required for both FcγR- and CR3-mediated engulfment in macrophages and for TCR internalization via phagocytic uptake of MHC from APCs, and the RhoG–ELMO1–Dock180 module drives dendritic spine morphogenesis in hippocampal neurons.

    Evidence Systematic RNAi screen of 20 Rho GTPases with FRET biosensor at phagocytic cups; siRNA knockdown and bead phagocytosis for TCR; RNAi screen of 70 GEFs for spine morphology

    PMID:21820331 PMID:21878497 PMID:21900250

    Open questions at the time
    • The identity of the GEF activating RhoG during FcγR/CR3 phagocytosis was not determined
    • How RhoG is spatially activated at both FcγR and CR3 cups despite different signaling cascades was unclear
  12. 2013 High

    RhoG knockout mice revealed a role in hemostasis: RhoG is activated downstream of GPVI–FcRγ in platelets via Src family kinases and is required for granule secretion (α, dense, lysosomal) and in vivo thrombus formation.

    Evidence RhoG−/− mice with platelet aggregation, secretion, integrin activation assays, pharmacological kinase inhibitors, in vivo thrombosis models

    PMID:24106269 PMID:24106270

    Open questions at the time
    • Which ELMO/Dock complex or alternative effector mediates RhoG function in platelets was not determined
    • Whether RhoG deficiency causes bleeding in humans was unknown
  13. 2014 High

    P-Rex1 was identified as a direct GEF for RhoG in GPCR-stimulated neutrophils, and RhoG was shown to recruit the Rac GEF DOCK2 to the leading edge, linking GPCR signaling through P-Rex1→RhoG→DOCK2→Rac to NADPH oxidase activation.

    Evidence In vitro GEF assay for P-Rex1 on RhoG, P-Rex1/RhoG double knockout neutrophils, DOCK2 recruitment imaging, NADPH oxidase activity

    PMID:24659802

    Open questions at the time
    • Whether P-Rex1 activates RhoG in other GPCR-responsive cell types was not tested
    • Structural basis for P-Rex1 selectivity toward RhoG was unknown
  14. 2021 High

    A direct role for RhoG in cytotoxic lymphocyte function was discovered: RhoG interacts with the exocytosis protein Munc13-4 and is required for docking and fusion of cytotoxic granules at the plasma membrane; biallelic RHOG mutations in human patients cause defective degranulation, establishing RHOG as a disease gene for immune deficiency.

    Evidence Patient genetic analysis with biallelic RHOG mutations, RHOG knockout in cell lines and primary CTLs, Co-IP of RhoG with Munc13-4, cytotoxic granule imaging and cytotoxicity assays

    PMID:33513601

    Open questions at the time
    • Whether the RhoG–Munc13-4 interaction is GTP-dependent was not fully resolved
    • The structural interface between RhoG and Munc13-4 is not mapped
    • Whether other exocytosis defects (e.g., platelet granule release) share this mechanism was not addressed
  15. 2024 High

    The structural mechanism by which RhoG activates Rac1 was resolved: cryo-EM of the DOCK5/ELMO1 complex revealed an autoinhibited closed conformation that RhoG converts to an open, catalytically active state by simultaneously contacting both ELMO1 and DOCK5, providing the allosteric mechanism for the GTPase cascade.

    Evidence Cryo-EM structures of free and RhoG/Rac1-bound DOCK5/ELMO1, SPR binding kinetics, in vitro Rac GEF activity assay

    PMID:38857861

    Open questions at the time
    • Whether this allosteric mechanism applies to all ELMO–Dock complexes (Dock180, Dock2, Dock3, Dock4) is assumed but not structurally confirmed
    • In vivo validation of the conformational switch is lacking
  16. 2024 Medium

    A mitotic function for RhoG was uncovered: Ephexin4 phosphorylation at Ser41 during M phase activates RhoG at the plasma membrane, and this is required for proper chromosome alignment and spindle assembly checkpoint satisfaction.

    Evidence Ephexin4 S41A/S41E knockdown-rescue, RhoG activity assay, chromosome alignment imaging, BubR1 kinetochore analysis

    PMID:39675713

    Open questions at the time
    • The kinase phosphorylating Ephexin4 at Ser41 was not identified
    • Whether RhoG's mitotic role operates through ELMO–Dock–Rac1 or a distinct effector is not defined
    • Independent replication is needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full spectrum of RhoG effectors beyond the ELMO–Dock–Rac axis, the structural basis for the RhoG–Munc13-4 and RhoG–PI3K interactions, how tissue-specific GEF utilization is determined, and whether RhoG deficiency underlies broader human immunodeficiency or hemostatic phenotypes.
  • No crystal or cryo-EM structure of RhoG bound to Munc13-4, kinectin, or PI3K exists
  • Tissue-specific knockout studies for most RhoG functions are lacking
  • The full clinical phenotype of human RHOG deficiency is not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 5 R-HSA-1266738 Developmental Biology 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-109582 Hemostasis 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1
Partners
DOCK180DOCK5ELMO1ELMO2KTN1SGEFTRIOUNC13D
Complex memberships
ELMO–DOCK5ELMO–Dock180 (Dock1)ELMO–Dock3ELMO–Dock4

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 RhoG interacts directly with Elmo in a GTP-dependent manner and forms a ternary complex with Dock180 to induce activation of Rac1; the RhoG-Elmo-Dock180 pathway is required for integrin-mediated Rac1 activation and cell spreading, as well as for NGF-induced neurite outgrowth. Co-IP, pulldown, dominant-negative rescue, RNAi knockdown, in vitro GEF assay Nature High 12879077
2000 Trio's N-terminal GEF domain (GEFD1/TrioD1) preferentially activates RhoG over Rac1 in vitro; TrioD1 controls a signaling cascade where RhoG activates Rac1 and Cdc42Hs, requiring the microtubule network and relocalizing RhoG to active sites at the plasma membrane. In vitro nucleotide exchange assay, dominant-negative epistasis, GFP-localization, co-expression experiments in fibroblasts Journal of cell science High 10652265 11146652
2000 Trio GEFD1 interacts through its PH domain with the actin-filament-crosslinking protein filamin, and localizes with endogenous filamin in HeLa cells; Trio GEFD1 induces actin-based ruffling in filamin-expressing but not filamin-deficient cells, placing filamin as a spatial scaffold downstream of Trio/RhoG signaling. Co-IP, filamin-deficient cell rescue, GFP colocalization, dominant-negative constructs Nature cell biology High 11146652
1998 Active RhoG produces cytoskeletal changes (ruffles, lamellipodia, filopodia, microvilli) that require endogenous Rac1 and Cdc42Hs activities; RhoG acts through a microtubule-dependent pathway that is distinct from growth-factor-stimulated Rac1/Cdc42Hs pathways, and RhoG does not directly interact with PAK-1, POR1, or WASP. Dominant-negative co-expression epistasis, GFP-tagged mutant proteins, nocodazole microtubule disruption, fluorescence microscopy Molecular biology of the cell High 9614181
2004 RhoG (and its C. elegans ortholog MIG-2) signals upstream of ELMO/CED-12 and Dock180 during phagocytosis of apoptotic cells; ARM repeats within CED-12/ELMO mediate interaction with activated RhoG, linking it to Dock180-dependent Rac activation and cytoskeletal reorganization during engulfment. Yeast two-hybrid, Co-IP, C. elegans genetic epistasis (loss-of-function), in vitro binding Current biology : CB High 15620647
1996 RhoGDI-3 is a GDP dissociation inhibitor that specifically interacts with GDP- and GTP-bound forms of RhoB and RhoG (but not RhoA, RhoC, or Rac1), inhibits GDP/GTP exchange on RhoB, and releases GDP-bound but not GTP-bound RhoB from cell membranes; RhoGDI-3 associates with a detergent-resistant membranous/cytoskeletal fraction. Yeast two-hybrid, in vitro GDP dissociation inhibition assay, membrane release assay, subcellular fractionation The Journal of biological chemistry High 8939998
2001 Kinectin is a key effector of RhoG; RhoG(GTP) specifically interacts with the central domain of kinectin, and RhoG co-localizes with kinectin and kinesin in the endoplasmic reticulum and lysosomes; anti-kinectin antibodies block RhoG morphogenic activity, and RhoG activation facilitates microtubule-dependent lysosomal transport through kinectin-kinesin. Yeast two-hybrid, co-precipitation, antibody microinjection, time-lapse videomicroscopy, GFP colocalization Molecular and cellular biology High 11689693
2002 RhoGDI-3 inhibits activation of RhoG and targets RhoG to the Golgi apparatus; the unique N-terminal amphipathic alpha-helical domain of RhoGDI-3 is required for Golgi targeting and for the stability of the cytoplasmic RhoG/RhoGDI-3 complex. Confocal microscopy, immuno-isolation, site-directed mutagenesis, GFP fusion constructs, in vitro GDI activity assay Traffic (Copenhagen, Denmark) High 11967128
2004 SGEF (SH3-containing GEF) specifically catalyzes nucleotide exchange on RhoG but not Rac1 or Rac3 in vitro; full-length SGEF activates RhoG in fibroblasts and induces dorsal membrane ruffles and macropinocytosis through a catalytically active DH domain. In vitro nucleotide exchange assay, dominant-active/catalytic-dead constructs, scanning electron microscopy, dextran uptake assay Molecular biology of the cell High 15133129
2004 Crystal structure of Trio N-terminal DH/PH domain (TrioN) resolved to 1.7 Å; RhoG is ~3× more efficiently exchanged than Rac by TrioN, with residues 54 and 69 (non-conserved between RhoG and Rac) responsible for GTPase specificity; the C-terminal basic tail of RhoG specifically assists TrioN-PH domain binding to PtdIns(3,4)P2 in vitro. X-ray crystallography, in vitro nucleotide exchange assay, mutagenesis, dot-blot phospholipid binding, affinity binding The Journal of biological chemistry High 15199069
2005 RhoG promotes cell migration by activating Rac1 through ELMO and Dock180; RhoG knockdown reduces Rac1 activation and lamellipodia formation at the leading edge in migrating HeLa cells; Dock180-Crk interaction is dispensable for RhoG-driven Rac1 activation and migration. RNAi knockdown, Transwell and scratch-wound migration assays, Rac1 pull-down activity assay, dominant-active/dominant-negative rescue Journal of cell science High 16339170
2007 RhoG is activated downstream of ICAM1 engagement in endothelial cells via the RhoG-specific GEF SGEF; ICAM1 binds SGEF through SGEF's SH3 domain; RhoG depletion decreases endothelial cup formation around adherent leukocytes and inhibits leukocyte trans-endothelial migration without affecting adhesion. RNAi knockdown (RhoG and SGEF), siRNA rescue, Co-IP, FRET-based activity assay, leukocyte TEM assay The Journal of cell biology High 17875742
2002 RhoG is activated by some Rac/Cdc42 GEFs (Vav2 and Dbs) in vitro, and GTP-loaded RhoG interacts with a specific subset of Rac/Cdc42 effectors (IQGAP2, MLK-3, PLD1) but not others (PAKs, POSH, WASP, Par-6, IRSp53); activated RhoG can induce lamellipodia independently of Rac1, suggesting direct effector usage. In vitro nucleotide exchange assay, GST pulldown with GTP-loaded RhoG, dominant-negative Rac1 Tat-fusion transduction, JNK/Akt activity assays The Journal of biological chemistry High 12376551
2002 Kalirin GEF1 domain activates RhoG to initiate new axon sprouting in sympathetic neurons; constitutively active RhoG mimics the Kalirin GEF1 phenotype, while RhoG inhibitors block it; dominant-negative Rac1, RhoA, and Cdc42 cannot block KalGEF1-driven axon sprouting. Microinjection, dominant-active/dominant-negative constructs, Kalirin antisense oligonucleotides, morphological analysis The Journal of neuroscience High 12177196
2002 Trio induces neurite outgrowth in PC12 cells via GEFD1-dependent activation of RhoG; the spectrin repeats and SH3-1 domain of Trio are required for GEFD1-mediated neurite outgrowth; Trio protein accumulates under NGF stimulation placing Trio upstream of RhoG in the NGF pathway. Dominant-negative and deletion mutant expression, NGF stimulation assays, PC12 differentiation Current biology : CB High 11864571
2002 Rac1 and RhoG can directly interact with phosphatidylinositol 3-kinase (PI3K) and stimulate Akt activity, protecting cells from UV-induced apoptosis; this survival function is independent of NF-κB transcription and JNK activation. Constitutively active mutant expression, co-immunoprecipitation with PI3K, Akt phosphorylation assays, UV apoptosis assay Oncogene Medium 11803464
2006 Dock4 is regulated by RhoG and its effector ELMO; active RhoG induces translocation of the Dock4-ELMO complex from cytoplasm to plasma membrane and enhances Dock4- and ELMO-dependent Rac1 activation and cell migration. Co-IP, Rac1 pull-down activity assay, GFP translocation imaging, RNAi knockdown, migration assay Experimental cell research Medium 17027967
2007 PLEKHG6 is a novel RhoG-specific GEF that is recruited by ezrin to the apical pole of epithelial cells; PLEKHG6 activates RhoG and forms a complex with ezrin and the RhoG effector ELMO; both PLEKHG6 and ezrin are required for macropinocytosis in EGF-stimulated epithelial cells. Co-IP, dominant-negative RhoG rescue, in vitro GEF activity assay, RNAi knockdown, dextran uptake assay Molecular biology of the cell High 17881735
2009 Syndecan-4 engagement by fibronectin activates PKCα, which triggers RhoG activation and subsequent dynamin- and caveolin-dependent α5β1-integrin endocytosis; RhoG gene disruption in mice retards dermal wound closure due to impaired fibroblast/keratinocyte migration. Atomic force microscopy, RhoG knockout mice, live imaging of integrin endocytosis, PKCα inhibition, caveolin/dynamin dominant-negative, wound healing assay Developmental cell High 21982645
2009 A syndecan-4–synectin–RhoGDI1 ternary complex maintains RhoG in an inactive state; PKCα phosphorylates RhoGDI1 at Ser96, triggering release of RhoG and enabling polarized Rac1 activation downstream of FGF2/syndecan-4 in endothelial cells. Co-IP, RhoGDI1 phosphorylation assay, FRET-based Rac1 activation biosensor, RhoGDI1 Ser96 mutagenesis, endothelial migration assay The Journal of cell biology High 19581409
2010 Ephexin4 is a GEF for RhoG that interacts with EphA2 in breast cancer cells; Ephexin4 acts downstream of EphA2 to promote ligand-independent cell migration and invasion via RhoG activation, which recruits ELMO2 and Dock4 to cortactin-rich protrusions; Dock4-mediated Rac activation is required for migration. Co-IP, RhoG pull-down activity assay, siRNA knockdown-rescue, GFP imaging of protrusions The Journal of cell biology High 20679435
2010 EGF stimulation leads to rapid RhoG activation in epithelial cells mediated primarily by Vav family GEFs (and partly PLEKHG6), as shown by nucleotide-free RhoG pulldown and siRNA knockdown of GEFs; EGF-induced RhoG and Rac1 activation are independent of each other; RhoG contributes to EGF-stimulated cell migration and EGF receptor internalization. Nucleotide-free RhoG pulldown activity assay, siRNA knockdown, pharmacological inhibitors, migration assay, receptor internalization assay Molecular biology of the cell High 20237158
2011 TC21 (Rras2) and RhoG are both required for TCR internalization from the immunological synapse via a phagocytic mechanism; TC21 co-translocates with the TCR to the IS, and both TC21 and RhoG are necessary for TCR-promoted uptake of MHC from antigen-presenting cells. siRNA knockdown, bead phagocytosis assay, live imaging, dominant-negative constructs Immunity High 21820331
2011 RhoG is required for particle uptake through both FcγR and CR3 in macrophages; RhoG is recruited and activated at phagocytic cups downstream of both receptors; FcγR-dependent engulfment requires Cdc42 and Rac2, CR3 requires RhoA, but RhoG is uniquely required by both pathways. RNAi screen of 20 Rho GTPases, FRET-based activation biosensor at phagocytic cup, fluorescence imaging Journal of cell science High 21878497
2011 The RhoG/ELMO1/Dock180 signaling module is required for dendritic spine morphogenesis in hippocampal neurons; depletion of Dock180, ELMO1, or RhoG each inhibit spine morphogenesis; overexpression of Dock180 promotes spine morphogenesis via Rac GTPase activation. RNAi screen of 70 Rho GEFs, siRNA knockdown of RhoG/ELMO1/Dock180, spine morphology quantification in hippocampal neurons The Journal of biological chemistry High 21900250
2012 RhoG is an inhibitor of neuronal process complexity regulated by miR-124; RhoG inhibits dendritic branching via a Cdc42-dependent mechanism and inhibits axonal branching via ELMO/Dock180/Rac1; miR-124 suppresses RhoG expression in neurons to promote process complexity. miR-124 overexpression/inhibition, shRNA knockdown, in vivo and in vitro hippocampal neuron morphology, epistasis with dominant-negative GTPase constructs The EMBO journal High 22588079
2014 P-Rex1 acts as a direct GEF for RhoG both in vitro and in GPCR-stimulated primary mouse neutrophils; loss of P-Rex1 or RhoG causes equivalent reductions in GPCR-driven Rac activation and NADPH oxidase activity; RhoG mediates Rac activation by recruiting the Rac GEF DOCK2 to the leading edge. In vitro GEF assay, P-Rex1/RhoG knockout neutrophils, DOCK2 recruitment imaging, NADPH oxidase activity assay, migration assay Journal of cell science High 24659802
2007 RhoG protects HeLa cells from anoikis through a PI3K-dependent mechanism; constitutively active RhoG binds the PI3K regulatory subunit p85α and induces Akt phosphorylation; this survival function is independent of ELMO- and Dock180-mediated Rac1 activation. RNAi knockdown, Co-IP with p85α, Akt phosphorylation assay, constitutively active/dominant-negative constructs, anchorage-independent assay Experimental cell research Medium 17570359
2006 RhoG deficiency in mice causes a marked impairment of GPCR-stimulated (C5a or fMLP) oxidant generation in neutrophils; early Rac1 and Rac2 activation by fMLP is diminished in RhoG-/- neutrophils; chemotaxis and bacterial killing are unaffected. RhoG knockout mice, NADPH oxidase activity assay, Rac1/Rac2 pull-down activity assay, chemotaxis assay Journal of immunology High 16621998
2009 Yersinia enterocolitica invasin activates RhoG at the contact site to promote cell invasion; the type III effector YopE acts as a GAP for RhoG to downregulate its activity; the RhoG-Elmo/Dock180 module controls both Rac1 activation and deactivation during Yersinia infection. FRET-based RhoG biosensor, siRNA knockdown, bacterial internalization assay, GAP activity assay Journal of cell science High 19208761
2009 Y. pseudotuberculosis invasin recruits RhoG to the site of bacterial attachment through high-affinity integrin engagement; RhoG inactivation reduces invasin-mediated internalization; YopE efficiently inactivates RhoG (as shown by FRET biosensor); YopT mislocalizes RhoG; RhoG activation can bypass a deficit in Rac1 activity for particle uptake. FRET-based RhoG activation biosensor, siRNA knockdown, bacterial internalization assay, GFP colocalization Infection and immunity High 19720752
2013 RhoG regulates platelet granule secretion (α-granules, dense granules, lysosomes) and thrombus formation downstream of GPVI (CRP) stimulation; RhoG-/- mice show reduced in vivo thrombus formation; integrin activation and aggregation defects can be rescued by ADP co-stimulation, indicating they are secondary to dense granule secretion deficiency. RhoG knockout mice, platelet aggregation assay, secretion assay, integrin activation assay, in vivo thrombosis model, in vitro flow chamber The Journal of biological chemistry High 24106270
2013 RhoG is expressed and activated in platelets downstream of GPVI–Fcγ receptor complex stimulation; CRP-induced RhoG activation requires Src family kinase activity but not Syk or PI3K; RhoG deficiency reduces Syk, Akt, and ERK phosphorylation and delays in vivo thrombotic occlusion. RhoG knockout mice, pull-down activity assay, pharmacological kinase inhibitors, aggregation and secretion assays, in vivo thrombosis The Journal of biological chemistry High 24106269
2015 ELMO2 simultaneously binds ILK and RhoG to form tripartite ERI complexes; in differentiated keratinocytes, ERI complexes modulate microtubule dynamics in an integrin-independent manner through Rac1 activation, which in turn phosphorylates stathmin and inactivates GSK-3β to stabilize microtubules. Co-IP, ILK gene knockout in keratinocytes, ELMO2 and RhoG overexpression, microtubule dynamics imaging, Rac1 activity assay, stathmin/GSK-3β phosphorylation Molecular biology of the cell High 25995380
2015 Active RhoG/MIG-2 directly binds to the actin-binding scaffold protein Anillin and recruits it to the leading edge during C. elegans neuronal migration and neurite growth; Anillin stabilizes F-actin at the leading edge by antagonizing Cofilin severing activity. C. elegans somatic CRISPR conditional mutations, biochemical pulldown, actin cosedimentation assay, live imaging of GFP-tagged proteins Current biology : CB Medium 25843030
2017 SGEF is the exchange factor responsible for RhoG activation during invadopodia disassembly in human breast cancer cells; RhoG and SGEF both promote invadopodia disassembly independently of Rac1, and modulate paxillin phosphorylation as part of the disassembly mechanism. siRNA knockdown (RhoG and SGEF), invadopodia lifetime assay, paxillin phosphorylation assay, constitutively active Rac1 rescue Journal of cell science Medium 28202690
2017 RhoG and its GEF Trio regulate circular dorsal ruffle (CDR) dynamics, macropinocytosis, receptor internalization, and cell migration downstream of PDGF in a PI3K- and Src-dependent manner; RhoG regulation of CDR area is independent of Rac1 function. siRNA knockdown, PI3K/Src inhibitors, dominant-active/dominant-negative constructs, CDR imaging, dextran uptake assay, migration assay Molecular biology of the cell Medium 28468978
2016 Tyrosine phosphorylation of SGEF at Tyr530 (within the DH domain) by Src suppresses SGEF's interaction with RhoG, RhoG activation, and SGEF-mediated promotion of cell migration; Y530F mutation blocks the inhibitory effect of Src on SGEF. Co-IP of SGEF with RhoG, RhoG pull-down activity assay, site-directed mutagenesis, Src kinase co-expression, migration assay PloS one Medium 27437949
2018 Ephexin4 forms an autoinhibited oligomer via an intermolecular interaction mediated by Glu295; this oligomerization impedes RhoG binding to Ephexin4 and reduces RhoG activation; Elmo reverses this autoinhibition to enhance Ephexin4 GEF activity. Ephexin4 point mutant (E295A) analysis, Co-IP of RhoG with Ephexin4 mutants, RhoG pull-down activity assay, phagocytosis assay, membrane ruffle formation assay Cells Medium 30445756
2021 RhoG deficiency in human lymphocytes impairs cytotoxic granule (CG) exocytosis; RhoG interacts with the exocytosis protein Munc13-4 (protein-protein interaction demonstrated), and this interaction is critical for docking of Munc13-4+ CGs to the plasma membrane and subsequent membrane fusion and CG content release. Patient genetic analysis (biallelic RHOG mutations), RHOG knockout in cell lines and primary CTLs, Co-IP of RhoG with Munc13-4, cytotoxic granule localization imaging, cytotoxicity assays Blood High 33513601
2024 Cryo-EM structures of DOCK5/ELMO1 alone and in complex with RhoG and Rac1 reveal that DOCK5/ELMO1 adopts a closed (autoinhibited) conformation; RhoG binds to both ELMO1 and DOCK5 and facilitates a closed-to-open conformational transition that enhances Rac GEF activity; SPR and biochemical assays confirm RhoG increases DOCK5/ELMO1 affinity for Rac1 and its GEF activity. Cryo-EM structure determination, surface plasmon resonance (SPR), in vitro Rac GEF activity assay, structural variability analysis The Journal of biological chemistry High 38857861
2024 Ephexin4 is phosphorylated at Ser41 exclusively during M phase; this phosphorylation is required for RhoG localization to the plasma membrane, chromosome alignment, and proper spindle assembly checkpoint satisfaction; phospho-mimetic S41E mutant enhances active RhoG levels. Ephexin4 knockdown-rescue with S41A/S41E mutants, RhoG pull-down activity assay, GFP-RhoG localization imaging, chromosome alignment/BubR1 kinetochore analysis, MDCK cyst morphogenesis assay The Journal of biological chemistry Medium 39675713
2006 RhoG is involved in caveolar endocytosis; activated RhoG(Q61L) localizes preferentially to endocytic vesicles decorated with caveola-derived markers and affects caveola internalization and subsequent delivery to the Golgi; this pathway depends on lipid raft integrity and dynamin2. GFP-tagged RhoG/Rac1 chimeras and effector mutants, caveolae internalization assay, siRNA knockdown, live imaging Oncogene Low 16568096
2009 RhoG promotes neural progenitor cell (NPC) proliferation in the ventricular zone during cortical development through a PI3K-dependent mechanism that does not require ELMO interaction; knockdown of RhoG suppresses BrdU incorporation and Ki67 positivity without affecting NPC differentiation or survival. Constitutively active/dominant-negative RhoG expression in vivo and in vitro, RNAi knockdown, BrdU/Ki67 proliferation assay, PI3K inhibitor Molecular biology of the cell Medium 19812248
2019 RhoG modulates focal adhesion (FA) dynamics by promoting microtubule-mediated FA disassembly; RhoG silencing increases FA stability, number, and size, and increases stress fiber thickness and contractility (blebbistatin-sensitive). siRNA knockdown, live FA dynamics imaging, FA quantification (number, size, lifetime), blebbistatin treatment, microtubule interference Scientific reports Medium 30914742
2019 In vascular endothelial cells, RHOG activates RAC1 through an intermediate step requiring CDC42; RHOG, CDC42, and RAC1 are each required for tube formation; p-ERK decreases upon knockdown of any of these GTPases, and ERK acts downstream of PI3K-RHOG-CDC42-RAC1. siRNA knockdown, dominant-active rescue constructs, PI3K/MAPK inhibitors, tube formation assay, p-ERK/p-AKT assays Cells Medium 30781697
2014 Arhgef16 interacts with Elmo1 and promotes clearance of apoptotic cells in a RhoG-dependent but Dock1-independent manner; Arhgef16-mediated engulfment increases synergistically with Elmo1 co-expression. Yeast two-hybrid screen, Co-IP in mammalian cells, phagocytosis assay, siRNA knockdown of RhoG/Dock1 Biochimica et biophysica acta Medium 25063526
2012 Dock3 forms a ternary complex with Elmo and activated RhoG downstream of BDNF-TrkB signaling to promote Rac1 activation and neurite outgrowth in PC12 cells; Dock3 phosphorylation is required for efficient Rac1 activation via this complex. Co-IP, Rac1 pull-down activity assay, phosphorylation analysis, dominant-active RhoG construct, neurite outgrowth assay Genes to cells Medium 22734669
2010 SNX1 and SNX2 interact directly with inactive RhoG and with the RhoG GEF Kalirin-7; co-overexpression of SNX1/2 and Kalirin-7 induces RhoG-dependent lamellipodia formation requiring functional PX and BAR domains of SNX; depletion of SNX1/2 inhibits Kalirin-7-mediated lamellipodia. Co-IP, siRNA knockdown, domain deletion mutants, lamellipodia formation assay, RhoG pull-down Traffic (Copenhagen, Denmark) Medium 20604901
2025 Mycobacterium tuberculosis serine protease Rv2569c interacts with RhoG in macrophages, blocking NF-κB signaling pathway initiation and suppressing NLRP3 inflammasome activation, thereby reducing IL-1β secretion and promoting mycobacterial survival; Rv2569c-deficient M.tb shows weakened inflammatory suppression. Co-IP (Rv2569c with RhoG), Rv2569c-deficient M.tb strain, NF-κB pathway assay, NLRP3/IL-1β measurement, in vitro and in vivo survival assay International journal of biological macromolecules Medium 40228763

Source papers

Stage 0 corpus · 80 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo. Nature 290 12879077
2000 The Rac1- and RhoG-specific GEF domain of Trio targets filamin to remodel cytoskeletal actin. Nature cell biology 184 11146652
2007 RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration. The Journal of cell biology 176 17875742
2004 Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. Current biology : CB 168 15620647
2011 T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis. Immunity 160 21820331
2000 TrioGEF1 controls Rac- and Cdc42-dependent cell structures through the direct activation of rhoG. Journal of cell science 150 10652265
2002 Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-kappaB. Oncogene 145 11803464
2005 Activation of Rac1 by RhoG regulates cell migration. Journal of cell science 144 16339170
1998 RhoG GTPase controls a pathway that independently activates Rac1 and Cdc42Hs. Molecular biology of the cell 135 9614181
2002 The Human Rho-GEF trio and its target GTPase RhoG are involved in the NGF pathway, leading to neurite outgrowth. Current biology : CB 134 11864571
2010 Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. The Journal of cell biology 126 20679435
2000 Small GTPase RhoG is a key regulator for neurite outgrowth in PC12 cells. Molecular and cellular biology 122 10982854
2011 A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis. Developmental cell 113 21982645
1996 RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG. The Journal of biological chemistry 109 8939998
1992 Growth-regulated expression of rhoG, a new member of the ras homolog gene family. Molecular and cellular biology 105 1620121
2012 miR-124-regulated RhoG reduces neuronal process complexity via ELMO/Dock180/Rac1 and Cdc42 signalling. The EMBO journal 92 22588079
2004 SGEF, a RhoG guanine nucleotide exchange factor that stimulates macropinocytosis. Molecular biology of the cell 92 15133129
2002 RhoG signals in parallel with Rac1 and Cdc42. The Journal of biological chemistry 91 12376551
1997 The small GTPases Cdc42Hs, Rac1 and RhoG delineate Raf-independent pathways that cooperate to transform NIH3T3 cells. Current biology : CB 89 9285711
2009 A cell active chemical GEF inhibitor selectively targets the Trio/RhoG/Rac1 signaling pathway. Chemistry & biology 87 19549603
2002 Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms. The Journal of neuroscience : the official journal of the Society for Neuroscience 80 12177196
2006 Dock4 is regulated by RhoG and promotes Rac-dependent cell migration. Experimental cell research 75 17027967
2009 Suppression of RhoG activity is mediated by a syndecan 4-synectin-RhoGDI1 complex and is reversed by PKCalpha in a Rac1 activation pathway. The Journal of cell biology 67 19581409
2001 Kinectin is a key effector of RhoG microtubule-dependent cellular activity. Molecular and cellular biology 66 11689693
2007 Interaction of ezrin with the novel guanine nucleotide exchange factor PLEKHG6 promotes RhoG-dependent apical cytoskeleton rearrangements in epithelial cells. Molecular biology of the cell 63 17881735
2012 The small GTPase RhoG mediates glioblastoma cell invasion. Molecular cancer 59 22966858
2011 RhoG is required for both FcγR- and CR3-mediated phagocytosis. Journal of cell science 58 21878497
2014 P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils. Journal of cell science 57 24659802
2004 Immunological function in mice lacking the Rac-related GTPase RhoG. Molecular and cellular biology 53 14701744
2015 Anillin Regulates Neuronal Migration and Neurite Growth by Linking RhoG to the Actin Cytoskeleton. Current biology : CB 51 25843030
2011 Ephexin4 and EphA2 mediate resistance to anoikis through RhoG and phosphatidylinositol 3-kinase. Experimental cell research 47 21621533
2011 The RhoG/ELMO1/Dock180 signaling module is required for spine morphogenesis in hippocampal neurons. The Journal of biological chemistry 44 21900250
2004 The C-terminal basic tail of RhoG assists the guanine nucleotide exchange factor trio in binding to phospholipids. The Journal of biological chemistry 44 15199069
2017 A RhoG-mediated signaling pathway that modulates invadopodia dynamics in breast cancer cells. Journal of cell science 43 28202690
2008 Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration. Journal of cell science 43 18505794
2021 RhoG deficiency abrogates cytotoxicity of human lymphocytes and causes hemophagocytic lymphohistiocytosis. Blood 42 33513601
2002 RhoGDI-3 regulates RhoG and targets this protein to the Golgi complex through its unique N-terminal domain. Traffic (Copenhagen, Denmark) 42 11967128
2010 Endogenous RhoG is rapidly activated after epidermal growth factor stimulation through multiple guanine-nucleotide exchange factors. Molecular biology of the cell 35 20237158
2006 Involvement of the Rho/Rac family member RhoG in caveolar endocytosis. Oncogene 35 16568096
2009 Yersinia enterocolitica differentially modulates RhoG activity in host cells. Journal of cell science 34 19208761
2006 RhoG regulates the neutrophil NADPH oxidase. Journal of immunology (Baltimore, Md. : 1950) 34 16621998
2019 RHOG Activates RAC1 through CDC42 Leading to Tube Formation in Vascular Endothelial Cells. Cells 31 30781697
2017 Regulation of circular dorsal ruffles, macropinocytosis, and cell migration by RhoG and its exchange factor, Trio. Molecular biology of the cell 31 28468978
2016 MicroRNA-124 Controls Transforming Growth Factor β1-Induced Epithelial-Mesenchymal Transition in the Retinal Pigment Epithelium by Targeting RHOG. Investigative ophthalmology & visual science 31 26746014
2009 Yersinia pseudotuberculosis virulence determinants invasin, YopE, and YopT modulate RhoG activity and localization. Infection and immunity 31 19720752
2007 RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism. Experimental cell research 31 17570359
2013 RhoG protein regulates platelet granule secretion and thrombus formation in mice. The Journal of biological chemistry 28 24106270
2017 GRHL2 suppresses tumor metastasis via regulation of transcriptional activity of RhoG in non-small cell lung cancer. American journal of translational research 27 28979695
2014 Arhgef16, a novel Elmo1 binding partner, promotes clearance of apoptotic cells via RhoG-dependent Rac1 activation. Biochimica et biophysica acta 27 25063526
2012 Dock3 regulates BDNF-TrkB signaling for neurite outgrowth by forming a ternary complex with Elmo and RhoG. Genes to cells : devoted to molecular & cellular mechanisms 26 22734669
2016 Involvement of Tiam1, RhoG and ELMO2/ILK in Rac1-mediated phagocytosis in human trabecular meshwork cells. Experimental cell research 25 27539661
2015 An ELMO2-RhoG-ILK network modulates microtubule dynamics. Molecular biology of the cell 25 25995380
2009 RhoG promotes neural progenitor cell proliferation in mouse cerebral cortex. Molecular biology of the cell 25 19812248
2013 RhoG protein regulates glycoprotein VI-Fc receptor γ-chain complex-mediated platelet activation and thrombus formation. The Journal of biological chemistry 18 24106269
2013 miR-124-regulated RhoG: A conductor of neuronal process complexity. Small GTPases 17 23303397
2021 miR‑124‑3p inhibits the viability and motility of glioblastoma multiforme by targeting RhoG. International journal of molecular medicine 16 33649803
2002 Developmental changes in expression of small GTPase RhoG mRNA in the rat brain. Brain research. Molecular brain research 16 12393274
2016 Design of novel lead molecules against RhoG protein as cancer target - a computational study. Journal of biomolecular structure & dynamics 15 27691842
2010 A novel, retromer-independent role for sorting nexins 1 and 2 in RhoG-dependent membrane remodeling. Traffic (Copenhagen, Denmark) 15 20604901
2022 RhoG's Role in T Cell Activation and Function. Frontiers in immunology 14 35280994
2016 Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity. Journal of neurochemistry 14 27412363
2019 RhoG and Cdc42 can contribute to Rac-dependent lamellipodia formation through WAVE regulatory complex-binding. Small GTPases 13 31451035
2016 RHOG-DOCK1-RAC1 Signaling Axis Is Perturbed in DHEA-Induced Polycystic Ovary in Rat Model. Reproductive sciences (Thousand Oaks, Calif.) 13 27662902
2016 Immunological and Functional Characterization of RhoGDI3 and Its Molecular Targets RhoG and RhoB in Human Pancreatic Cancerous and Normal Cells. PloS one 13 27832197
2021 In silico identification and characterization of small-molecule inhibitors specific to RhoG/Rac1 signaling pathway. Journal of biomolecular structure & dynamics 12 34877916
2019 The small GTPase RhoG regulates microtubule-mediated focal adhesion disassembly. Scientific reports 12 30914742
2012 RRas2, RhoG and T-cell phagocytosis. Small GTPases 12 22790196
2023 Role of RhoG as a regulator of cellular functions: integrating insights on immune cell activation, migration, and functions. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 8 37378671
2018 The Intermolecular Interaction of Ephexin4 Leads to Autoinhibition by Impeding Binding of RhoG. Cells 8 30445756
2016 Tyrosine Phosphorylation of SGEF Regulates RhoG Activity and Cell Migration. PloS one 8 27437949
2018 RhoG-ELMO1-RAC1 is involved in phagocytosis suppressed by mono-butyl phthalate in TM4 cells. Environmental science and pollution research international 7 30350139
1997 Structure of the human ARHG locus encoding the Rho/Rac-like RhoG GTPase. Genomics 7 9177787
2021 RhoG-Rac1 Signaling Pathway Mediates Metabolic Dysfunction of the Pancreatic Beta-Cells Under Chronic Hyperglycemic Conditions. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 6 33851799
2023 RhoG-Binding Domain of Elmo1 Ameliorates Excessive Process Elongation Induced by Autism Spectrum Disorder-Associated Sema5A. Pathophysiology : the official journal of the International Society for Pathophysiology 5 38133141
2019 RhoG/Rac1 signaling pathway involved in migration and invasion of salivary adenoid cystic carcinoma cells. Oral diseases 5 31793126
2024 RhoG facilitates a conformational transition in the guanine nucleotide exchange factor complex DOCK5/ELMO1 to an open state. The Journal of biological chemistry 3 38857861
2024 Phosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division. The Journal of biological chemistry 3 39675713
2010 Bayesian integrated modeling of expression data: a case study on RhoG. BMC bioinformatics 2 20515463
2026 [Retracted] miR‑124‑3p inhibits the viability and motility of glioblastoma multiforme by targeting RhoG. International journal of molecular medicine 0 41614420
2025 Serine protease Rv2569c inhibits inflammatory response and promotes intracellular survival of Mycobacterium tuberculosis by targeting the RhoG-NF-κB-NLRP3 pathway. International journal of biological macromolecules 0 40228763