Affinage

RHOQ

Rho-related GTP-binding protein RhoQ · UniProt P17081

Length
205 aa
Mass
22.7 kDa
Annotated
2026-04-28
48 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RHOQ (TC10) is a Rho-family small GTPase that cycles between GTP-bound active and GDP-bound inactive states to control membrane trafficking, cortical actin remodeling, and signal transduction across adipocytes, neurons, endothelial cells, and immune cells. In adipocytes, insulin activates RHOQ via the CAP/Cbl/CrkII/C3G pathway at caveolin-enriched lipid raft microdomains—where caveolin-1 stabilizes its GDP-bound state—to drive GLUT4 vesicle translocation through effectors including CIP4/2, the Par6-Par3-aPKCζ polarity complex, and Exo70 of the exocyst, independently of PI3K (PMID:11309621, PMID:14734537, PMID:12242347, PMID:22900022). In neurons, locally translated RHOQ on Rab11-positive recycling endosomes promotes Exo70-dependent membrane expansion at growth cones for axon elongation and specification, regulates microtubule stability via a PAK2-JNK pathway, and activates collybistin by relieving its autoinhibition to promote gephyrin clustering at inhibitory synapses (PMID:19846717, PMID:24223996, PMID:40008675, PMID:24297911, PMID:35989712). Spatial regulation of RHOQ activity is achieved through CDK5-dependent Thr197 phosphorylation that retains it in lipid rafts, p190B RhoGAP-mediated inactivation downstream of cAMP-PKA signaling, and palmitoylation-dependent trafficking through the secretory pathway (PMID:18948252, PMID:29072354, PMID:12529401).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1998 High

    Establishing that TC10 is a functional Rho-family GTPase with defined effector specificity answered whether this orphan GTPase had signaling capacity: TC10 activates JNK and PAK and engages αPAK, βPAK, γPAK, MRCKα/β, MLK2, and N-WASP in a GTP-dependent manner, distinguishing its effector spectrum from Cdc42.

    Evidence In vitro GTPase assays, effector binding assays, JNK/PAK kinase assays, yeast two-hybrid

    PMID:9799731

    Open questions at the time
    • No physiological context for effector engagement identified
    • Upstream activating signals unknown
  2. 1999 High

    Demonstrating that constitutively active TC10 drives filopodia, transcriptional activation (JNK, SRF, NF-κB), and cellular transformation established TC10 as a bona fide signaling GTPase with oncogenic potential, while identification of Borg proteins as negative regulators revealed a first layer of regulatory control.

    Evidence Gain/loss-of-function mutants, reporter assays, transformation assays, yeast two-hybrid, GST pulldowns

    PMID:10445846 PMID:10490598

    Open questions at the time
    • Physiological stimulus for TC10 activation not yet identified
    • In vivo relevance of transformation activity uncharacterized
  3. 2001 High

    Connecting insulin signaling to TC10 activation via the CAP/Cbl/CrkII/C3G pathway at lipid raft microdomains resolved how TC10 is physiologically activated and established its essential role in PI3K-independent GLUT4 translocation in adipocytes.

    Evidence Dominant-negative mutants, lipid raft fractionation, TC10/H-Ras and K-Ras chimeras, GLUT4 translocation and glucose uptake assays in 3T3-L1 adipocytes

    PMID:11309621 PMID:11502760

    Open questions at the time
    • Direct GEF-substrate biochemistry for C3G-TC10 not shown
    • Downstream effectors mediating GLUT4 translocation not yet mapped
  4. 2002 High

    Identification of CIP4/2 as a TC10 effector required for GLUT4 translocation, and demonstration that TC10α and TC10β have isoform-specific effects on cortical actin, began to define the downstream effector logic: TC10α uniquely disrupts cortical actin through its N-terminal extension while both isoforms are insulin-activated at lipid rafts.

    Evidence Dominant-active/negative TC10 mutants, CIP4/2 translocation imaging, GLUT4 assays, isoform comparison, Xenopus extract actin polymerization, COPI binding in 3T3-L1 adipocytes

    PMID:11821390 PMID:12134073 PMID:12242347

    Open questions at the time
    • Whether CIP4/2 directly bridges TC10 to GLUT4 vesicle fusion machinery unknown
    • Structural basis of isoform-specific actin effects unresolved
  5. 2003 High

    Mapping the N-terminal extension GAG/GPG motifs as responsible for lipid-raft-targeted cortical actin disruption, showing palmitoylation at C209 is required for raft localization, and demonstrating TC10-dependent PtdIns-3-P production collectively defined the domain architecture and lipid requirements for TC10 function in adipocytes, while revealing cell-type specificity (TC10 dispensable for GLUT4 in myocytes).

    Evidence Systematic chimera/mutagenesis, BFA/temperature blocks, lipid mass spectrometry, GLUT4 assays in adipocytes vs L6 myocytes

    PMID:12529401 PMID:12912916 PMID:12972548 PMID:14615606

    Open questions at the time
    • Identity of the kinase/enzyme generating PtdIns-3-P downstream of TC10 unknown
    • Mechanism of cell-type specificity not molecularly explained
  6. 2004 High

    Demonstrating that activated TC10 recruits PKCζ/λ to lipid rafts through the Par6-Par3 polarity complex, leading to PI3K-independent GSK-3β phosphorylation, identified a second major signaling branch downstream of TC10 in insulin action.

    Evidence Co-immunoprecipitation, kinase assays, Clostridium difficile toxin B treatment, immunofluorescence in adipocytes

    PMID:14734537

    Open questions at the time
    • Whether Par6-aPKC pathway contributes to GLUT4 translocation or only GSK-3β phosphorylation unclear
    • How Par6-Par3 are recruited to TC10 not structurally resolved
  7. 2007 High

    FRET/FLIM detection of a TC10-Exo70 complex at membrane protrusions that antagonizes Cdc42/N-WASP-driven actin polymerization established TC10's role in neurite extension and revealed functional antagonism between TC10 and Cdc42 at protrusion sites.

    Evidence FRET/FLIM in living PC12 cells, siRNA knockdown of Cdc42 and Exo70, N-WASP FRET biosensor

    PMID:17635999

    Open questions at the time
    • Whether TC10 directly inhibits N-WASP or acts through Exo70 sequestration unresolved
    • Relevance in primary neurons not tested
  8. 2008 High

    Discovery that CDK5 phosphorylates TC10 at Thr197 in a Fyn-dependent manner to retain it in lipid rafts and promote cortical actin depolymerization revealed a post-translational mechanism controlling TC10 spatial regulation.

    Evidence T197A/T197D mutagenesis, CDK5 siRNA, olomoucine inhibitor, lipid raft fractionation, cortical actin imaging in adipocytes

    PMID:18948252

    Open questions at the time
    • Phosphatase that reverses Thr197 phosphorylation not identified
    • Whether CDK5-TC10 axis operates in neurons as well as adipocytes unknown
  9. 2009 High

    Establishing TC10 and Exo70 as essential for membrane addition at growth cones and polarized IGF-1R insertion for axon specification, plus identifying obscurin as a TC10-specific GEF in myoblasts, extended TC10 function beyond adipocytes to neuronal polarity and myofibril assembly.

    Evidence siRNA knockdown of TC10/Exo70, membrane expansion assays in hippocampal neurons; direct binding assays and shRNA in human skeletal myoblasts

    PMID:19258391 PMID:19846717

    Open questions at the time
    • Whether obscurin-TC10 operates in mature muscle in vivo unknown
    • How TC10-Exo70 coordinates with polarity pathways (Par3/Par6) in neurons unclear
  10. 2012 High

    Demonstrating that caveolin-1 binds GDP-TC10 and stabilizes the inactive state identified a tonic negative regulator that sets the activation threshold for TC10 at lipid rafts.

    Evidence In vitro nucleotide exchange kinetics, Cav1 siRNA, TC10 activity assays in 3T3-L1 adipocytes

    PMID:22900022

    Open questions at the time
    • Structural basis of caveolin-1 GDP-state stabilization unknown
    • Whether caveolin-1 regulation applies to TC10 in non-adipocyte contexts untested
  11. 2013 High

    Two advances redefined TC10 signaling dynamics: (1) GTP-bound TC10 binds collybistin's PH domain to relieve autoinhibition and promote gephyrin clustering at inhibitory synapses, establishing TC10 as a synaptic organizer; (2) GTP hydrolysis (inactivation) of TC10 at the plasma membrane, rather than its GTP-bound state, drives vesicle fusion and neurite outgrowth, revealing that the GTPase cycle itself is the functional signal.

    Evidence Yeast two-hybrid, Co-IP, electrophysiology (mIPSCs) in neurons; FRET-based TC10 biosensors, knockdown/rescue in hippocampal neurons and PC12 cells

    PMID:24223996 PMID:24297911

    Open questions at the time
    • Whether GTP hydrolysis timing is regulated by a specific GAP at growth cones unknown
    • In vivo validation of collybistin-TC10 at inhibitory synapses lacking
  12. 2014 High

    Discovery that local (intra-axonal) translation of TC10 mRNA via PI3K-Rheb-mTOR is required for membrane expansion established that TC10 availability is controlled at the translational level in axons, while RNA editing (A-to-I, N136S) that increases GTPase activity and invasion in colorectal cancer revealed a disease-relevant gain-of-function mechanism.

    Evidence Axon-specific TC10 mRNA knockdown, mTOR inhibitors, membrane expansion assay in DRG neurons; whole-genome/transcriptome sequencing, GTPase assays, invasion assays in CRC cells

    PMID:24663214 PMID:24667291

    Open questions at the time
    • Whether RNA editing of RHOQ occurs in normal tissues unknown
    • Translational regulation mechanism (IRES, UTR elements) not characterized
  13. 2017 High

    Two studies expanded TC10 biology to immune function and identified the GAP pathway controlling neurite outgrowth: TC10 knockout mice showed impaired germinal center B cell responses with partial functional redundancy with Cdc42, while cAMP-PKA was shown to inactivate TC10 at neurite tips via the STEF-Rac1-p190B RhoGAP cascade.

    Evidence TC10 knockout and TC10/Cdc42 double knockout mice, immunization, B cell assays; FRET TC10 biosensors, siRNA of p190A/p190B/STEF/Rac1 in PC12 cells

    PMID:28747344 PMID:29072354

    Open questions at the time
    • Downstream effectors of TC10 in B cells not identified
    • Whether p190B is the only GAP for TC10 in neurons unknown
  14. 2018 High

    Placing TC10 downstream of Arhgef7 (βPix) in axon specification via epistasis provided a second GEF-TC10 axis (alongside obscurin and C3G) and confirmed TC10's role in cortical neuron polarization in vivo.

    Evidence Arhgef7 knockdown rescued by constitutively active TC10, in utero electroporation, neuronal culture in cortical neurons

    PMID:29891904

    Open questions at the time
    • Whether Arhgef7 directly catalyzes TC10 nucleotide exchange not biochemically demonstrated
    • How Arhgef7-TC10 pathway intersects with Par3/Par6 in polarity unclear
  15. 2020 High

    Two discoveries placed TC10 in new signaling contexts: RHOQ is a DLL4/Notch transcriptional target that feeds forward to promote NICD nuclear translocation (loss causes autophagy-lysosomal degradation of Notch1) in endothelial cells, and Reelin activates TC10 via Cdc42 to drive VAMP7-vesicle fusion during DRG axon regeneration.

    Evidence RHOQ siRNA/overexpression, Notch reporters, autophagy inhibitors, in vivo angiogenesis; TC10 activity assays, VAMP7 colocalization, DRG axotomy

    PMID:32506201 PMID:32652719

    Open questions at the time
    • Mechanism by which TC10 prevents Notch1 autophagy unclear
    • Whether Reelin-Cdc42-TC10 cascade is direct or involves intermediate GEFs unknown
  16. 2021 High

    Demonstration that TC10 controls MT1-MMP surface exposure at invadopodia via a p190RhoGAP-TC10-Exo70 pathway established TC10 as a regulator of protease-dependent ECM degradation in breast cancer invasion.

    Evidence TC10 knockdown, FRET biosensor, MT1-MMP surface assay, ECM degradation, p190RhoGAP manipulation in breast cancer cells

    PMID:34531530

    Open questions at the time
    • Whether this pathway is active in non-cancerous cells undergoing invasion/migration unknown
    • Specificity for MT1-MMP versus other MMPs not tested
  17. 2022 High

    FRET-based conformational analysis revealed that TC10 uniquely opens autoinhibited (closed) collybistin, whereas Cdc42 only binds forced-open collybistin, providing a structural rationale for TC10's non-redundant role at inhibitory synapses.

    Evidence Time-resolved fluorescence FRET with collybistin conformational sensors, open/closed state mutagenesis, TC10 vs Cdc42 comparison

    PMID:35989712

    Open questions at the time
    • Atomic-resolution structure of TC10-collybistin complex not available
    • Whether TC10-collybistin is regulated by specific neuronal signals in vivo unknown
  18. 2025 High

    TC10 on Rab11-positive recycling endosomes was shown to regulate microtubule stability in axons via a PAK2-JNK signaling cascade that phosphorylates SCG10 and MAP1B, revealing an unexpected function in cytoskeletal dynamics beyond membrane trafficking.

    Evidence TC10 knockout neurons, PAK inhibitors, Rab11 colocalization, phospho-protein analysis, MKK4/MKK7 epistasis

    PMID:40008675

    Open questions at the time
    • How TC10 recruits or activates PAK2 on endosomes mechanistically unresolved
    • Whether microtubule regulation by TC10-PAK2-JNK operates in non-neuronal cells unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full structural basis of TC10 effector selectivity versus Cdc42, the identity of GAPs that terminate TC10 signaling at growth cones, the physiological relevance of RHOQ RNA editing, and how TC10's multiple upstream activators (C3G, obscurin, Arhgef7, Cdc42) are coordinated in different cell types.
  • No crystal structure of TC10 with any effector
  • No unifying model for how different GEFs are selected in different tissues
  • In vivo genetic evidence for TC10 in insulin-stimulated glucose uptake in adipose tissue lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3 GO:0008092 cytoskeletal protein binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-112316 Neuronal System 3 R-HSA-1266738 Developmental Biology 3 R-HSA-382551 Transport of small molecules 3
Partners
ARHGAP5ARHGEF9CAV1CDK5CIP4EXOC7PARD6APRKCZ
Complex memberships
Par6-Par3-aPKC polarity complexexocyst complex (via Exo70)

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Insulin activates TC10 (RHOQ) via the CAP/Cbl/CrkII/C3G pathway at lipid rafts, independent of PI3K, and this activation is essential for insulin-stimulated GLUT4 translocation in adipocytes. Dominant-negative mutants, lipid raft fractionation, glucose uptake assays in 3T3-L1 adipocytes Nature High 11309621
2001 TC10 localization to caveolin-enriched lipid raft microdomains (via the secretory trafficking pathway) is required for insulin-induced activation and GLUT4 translocation; TC10 directed to non-raft domains (K-Ras chimera) cannot be activated by insulin and does not inhibit GLUT4 translocation. TC10/H-Ras and TC10/K-Ras chimeras, dominant-interfering caveolin 3 mutant, lipid raft fractionation, GLUT4 translocation assays The Journal of cell biology High 11502760
1998 TC10 stimulates JNK and PAK activities and interacts with effectors including αPAK, βPAK, γPAK, MRCKα/β, MLK2, N-WASP, and MSE55 in a GTP-dependent manner; it does not interact with MLK3, WASP, or ACK-1, and is regulated by p50RhoGAP with lower affinity but greater responsiveness than Cdc42. In vitro GTPase assays, effector binding assays, JNK and PAK activity assays, yeast two-hybrid Current biology High 9799731
1999 Constitutively active TC10 (Q75L) stimulates filopodia formation, activates JNK and SRF-dependent transcription, activates NF-κB, and synergizes with activated Raf to transform NIH3T3 cells; TC10 also interacts with profilin in two-hybrid and in vitro binding assays; carboxyl-terminal prenylation is required for proper function. Gain-of-function/loss-of-function mutant expression, reporter assays, transformation assays, yeast two-hybrid, in vitro binding assay Oncogene High 10445846
1999 Borg proteins (Borg1, Borg2, Borg4, Borg5) interact with both TC10 and Cdc42 in a GTP-dependent manner requiring an intact CRIB domain; Borg3 binds only Cdc42, not TC10; Borgs function as negative regulators of Rho GTPase signaling. Yeast two-hybrid, GST pulldown assays, dominant-negative overexpression, cell spreading assays Molecular and cellular biology High 10490598
2001 PIST (a PDZ/coiled-coil domain protein) interacts directly and specifically with GTP-bound TC10 via TC10's effector binding domain; mutation within the effector binding domain of TC10 disrupts the interaction; PIST forms homodimers via the leucine zipper. Yeast two-hybrid, co-immunoprecipitation, in vitro binding, deletion/mutagenesis analysis Biochemical and biophysical research communications Medium 11162552
2002 CIP4/2 (Cdc42-interacting protein 4/2) is a TC10 effector: CIP4/2 translocates from intracellular compartments to the plasma membrane upon insulin stimulation in a TC10-dependent manner, and overexpression of CIP4/2 mutants with diminished TC10 binding inhibits insulin-stimulated GLUT4 translocation. Dominant-active and dominant-negative TC10 overexpression, GLUT4 translocation assays, subcellular localization imaging in 3T3-L1 adipocytes Proceedings of the National Academy of Sciences of the United States of America High 12242347
2002 Constitutively active TC10 (Q75L) induces actin comet tails in Xenopus oocyte extracts in vitro and perinuclear actin polymerization in adipocytes, while also disrupting cortical actin through its amino-terminal extension in a lipid-raft-targeted manner; TC10 binds directly to Golgi COPI coat proteins via a dilysine motif in its C-terminal domain and regulates vesicle trafficking. Xenopus oocyte extract actin polymerization assay, live cell imaging, deletion mutants, direct binding to COPI, VSV-G trafficking assay Molecular biology of the cell High 12134073
2003 Insulin-induced PtdIns-3-P formation in adipocytes occurs downstream of TC10 activation at lipid raft subdomains of the plasma membrane; exogenous PtdIns-3-P promotes GLUT4 plasma membrane translocation. Lipid mass spectrometry, dominant-negative and constitutively active TC10 mutants, GLUT4 translocation assays in insulin-responsive cells The EMBO journal Medium 12912916
2003 Lipid raft targeting of the TC10 amino-terminal extension (not the effector domain) is responsible for disruption of adipocyte cortical actin and inhibition of GLUT4 translocation; specific GAG and GPG sequences within the N-terminal extension are required; TC10β lacks these sequences and does not disrupt cortical actin. TC10/H-Ras and TC10/K-Ras chimeras, site-directed mutagenesis, deletion mutants, cortical actin imaging and GLUT4 translocation assays Molecular biology of the cell High 12972548
2003 TC10 trafficking to lipid raft microdomains requires transport through the secretory membrane system; C209 palmitoylation site is required for lipid raft localization; TC10 can also reach the plasma membrane via a classical secretory pathway-independent route. Point mutants (C206S, C209S), brefeldin A and 19°C temperature block, lipid raft fractionation, live cell imaging in adipocytes Molecular and cellular biology High 12529401
2004 Activated TC10 recruits PKCζ/λ to plasma membrane lipid raft microdomains through an indirect association with the Par6-Par3 protein complex, leading to activation loop phosphorylation of PKCζ; this TC10-Par6-aPKC pathway mediates insulin-stimulated GSK-3β phosphorylation independently of PI3K. Co-immunoprecipitation, constitutively active and dominant-negative TC10 expression, immunofluorescence, kinase activity assays, Clostridium difficile toxin B treatment in adipocytes The Journal of cell biology High 14734537
2003 TC10α is expressed and activated by insulin in adipocytes but its dominant-negative form does not inhibit insulin-induced actin remodeling or GLUT4 recruitment in myocytes, demonstrating cell-type specificity; Rac, not TC10, governs actin remodeling in muscle cells. Dominant-negative TC10 overexpression, RT-PCR, Western blot, immunofluorescence, GLUT4 surface labeling in L6 myoblasts/myotubes and 3T3-L1 adipocytes Molecular endocrinology High 14615606
2008 CDK5 phosphorylates TC10α on Thr197 in lipid raft domains downstream of Fyn-dependent Tyr15 phosphorylation of CDK5; this phosphorylation maintains TC10α in lipid rafts and promotes cortical actin depolymerization; dephosphorylation of TC10α (T197A) excludes it from lipid rafts and prevents these effects. Site-directed mutagenesis (T197A, T197D), CDK5 siRNA knockdown, kinase inhibitor (olomoucine), lipid raft fractionation, cortical actin imaging, GLUT4 translocation assays The Journal of biological chemistry High 18948252
2009 TC10 is activated by IGF-1 in hippocampal neurons and triggers translocation of the exocyst component Exo70 to the plasma membrane in distal axons and growth cones; TC10 and Exo70 are both required for membrane addition at the growth cone and for axon elongation; TC10 and Exo70 are also required for polarized insertion of IGF-1 receptor into one neurite to specify axon identity. siRNA knockdown of TC10 and Exo70, dominant-negative mutants, live imaging, membrane expansion assays in hippocampal neurons and isolated growth cones The Journal of neuroscience High 19846717
2009 Obscurin (a sarcomere-associated protein) directly binds TC10 via its RhoGEF motif and specifically activates TC10 (but not Rac or Cdc42); TC10 appears during differentiation of human skeletal myoblasts; inhibition or knockdown of TC10 blocks myofibril assembly. Co-immunoprecipitation, direct binding assays, shRNA knockdown, dominant-negative expression, myofibril assembly imaging in primary human skeletal myoblasts Journal of cell science High 19258391
2013 GTP-bound TC10 binds to the pleckstrin homology domain of collybistin (Cb), relieving its autoinhibition to promote gephyrin clustering at inhibitory synapses; constitutively active TC10 increases density of synaptic gephyrin clusters and mIPSC amplitudes, while dominant-negative TC10 has opposite effects; this does not require Cb's GEF activity. Yeast two-hybrid, co-immunoprecipitation, dominant-active and dominant-negative TC10 expression in neurons, electrophysiology (mIPSC recording), immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 24297911
2013 GTP hydrolysis (inactivation) of TC10 at the plasma membrane, rather than active TC10, promotes neurite outgrowth by releasing Exo70 and accelerating vesicle fusion; TC10 resides on Rab11-positive recycling endosomes and L1-positive vesicles that fuse to the plasma membrane at growth cones. FRET-based TC10 activity biosensors, TC10 knockdown, constitutively active TC10 rescue assays, colocalization analyses, live imaging in hippocampal neurons and NGF-treated PC12 cells PloS one High 24223996
2014 Intra-axonal synthesis of TC10 protein (local translation) is required for membrane expansion and axon outgrowth in DRG axons in response to NGF; local TC10 synthesis is triggered by PI3K-dependent Rheb-mTOR pathway activation simultaneously with Par3 local translation. Axon-specific TC10 mRNA knockdown, mTOR/PI3K inhibitors, membrane expansion assay, axon outgrowth assay in DRG neurons Nature communications High 24667291
2014 RNA editing of RHOQ (A-to-I, N136S substitution) increases RhoQ GTPase activity, promotes actin cytoskeletal reorganization, and enhances invasion potential in colorectal cancer cells; KRAS mutation further amplifies invasion potential of the N136S variant. Whole-genome and transcriptome sequencing, GTPase activity assays, actin staining, Transwell invasion assays, KRAS mutant co-expression The Journal of experimental medicine High 24663214
2007 NGF induces formation of an Exo70-TC10 complex (detected by FRET/FLIM) that locally antagonizes Cdc42-mediated N-WASP activation at membrane protrusions in PC12 cells; Exo70 targets the complex to protrusion sites and the complex suppresses N-WASP-driven actin polymerization. FRET imaging by fluorescence lifetime microscopy (FLIM), dominant-negative expression, siRNA knockdown of Cdc42 and Exo70, N-WASP activation FRET biosensor Journal of cell science High 17635999
2020 RHOQ is induced by DLL4/Notch signaling in endothelial cells and is essential for NICD nuclear translocation; loss of RHOQ targets Notch1 for autophagy-lysosomal degradation and sequesters NICD from the nucleus, creating a feed-forward regulatory loop. RHOQ siRNA knockdown, overexpression, in vitro angiogenesis assays, in vivo vessel formation, Notch signaling reporters, autophagy pathway inhibitors, subcellular fractionation Angiogenesis High 32506201
2012 Caveolin 1 binds GDP-bound TC10 and stabilizes the GDP-bound (inactive) state; knockdown of Caveolin 1 increases basal TC10 activity, indicating that Caveolin 1 maintains TC10 in an inactive state in unstimulated adipocytes. In vitro nucleotide exchange kinetics, co-immunoprecipitation, Caveolin 1 siRNA knockdown, TC10 activity assays in 3T3-L1 adipocytes PloS one High 22900022
2018 Arhgef7 (βPix) promotes axon formation upstream of TC10 in cortical neurons; expression of constitutively active TC10 rescues axon formation in Arhgef7-deficient neurons, placing TC10 downstream of Arhgef7 in axon specification. Genetic epistasis (Arhgef7 knockdown + active TC10 rescue), in utero electroporation in developing cortex, neuronal culture imaging Scientific reports High 29891904
2017 TC10 (RhoQ) is required for germinal center B cell responses and IgM production after immunization; TC10 can compensate for loss of Cdc42 in TLR-induced B cell activation and proliferation, indicating partial functional redundancy between TC10 and Cdc42 in B cells. TC10-deficient mouse model, TC10/Cdc42 double knockout mouse, in vivo immunization, in vitro BCR signaling and proliferation assays Journal of immunology High 28747344
2017 cAMP-induced PKA activation leads to TC10 inactivation at the plasma membrane via the STEF-Rac1-p190B RhoGAP pathway; p190B (but not p190A) mediates TC10 inactivation and RhoA inactivation; local TC10 inactivation at extending neurite tips is required for cAMP-induced neurite outgrowth. FRET-based TC10 activity biosensors, dominant-negative and constitutively active mutants, siRNA knockdown (p190A, p190B, STEF, Rac1), cAMP treatment in PC12 cells Genes to cells High 29072354
2021 TC10 is required for MT1-MMP surface exposure at invadopodia in breast cancer cells; TC10 activity at invadopodia is regulated by p190RhoGAP; TC10 controls MT1-MMP-driven ECM degradation through a p190RhoGAP-TC10-Exo70 pathway. TC10 knockdown, FRET biosensor for TC10 activity, MT1-MMP surface exposure assay, ECM degradation assay, p190RhoGAP overexpression/knockdown, Exo70 interaction studies Communications biology High 34531530
2022 TC10 (RhoQ) binds to closed/inactive collybistin and relieves its autoinhibition, switching it to an open/active state; this mechanism is distinct from Cdc42, which only interacts with forced-open collybistin; FRET measurements show TC10 binding changes collybistin conformational dynamics. Time-resolved fluorescence FRET measurements with collybistin FRET sensors, mutagenesis to force open/closed states, comparison of TC10 vs Cdc42 interaction Frontiers in synaptic neuroscience High 35989712
2025 TC10 on recycling endosomes (Rab11-positive) regulates microtubule stability and dynamics in axons via a PAK2-JNK pathway; TC10 promotes PAK2 localization to endosomes; TC10 loss reduces PAK2 autophosphorylation and JNK phosphorylation, leading to decreased phosphorylation of microtubule-binding proteins SCG10 and MAP1B, resulting in reduced microtubule stability and axon retraction. TC10 knockout neurons, PAK inhibitors, colocalization with Rab11, phospho-protein analysis, MKK4/MKK7 epistasis, JIP1 colocalization Journal of cell science High 40008675
2020 Reelin activates TC10 in DRG neurons via Cdc42; TC10 is required for DRG axon development; Reelin stimulates fusion of VAMP7-containing vesicles that co-contain TC10 to promote membrane addition during axon regeneration. TC10 activity assays, dominant-negative TC10, VAMP7 colocalization, DRG axotomy/regeneration assays, Cdc42 manipulation Journal of neuroscience research Medium 32652719
2002 TC10α and TC10β are both activated by insulin via the CAP/Cbl pathway in 3T3-L1 adipocytes; both localize to lipid rafts; however, TC10α overexpression disrupts cortical actin and fully blocks glucose transport, while TC10β has little effect on cortical actin and only partially inhibits glucose transport, demonstrating isoform-specific downstream effects. cDNA cloning, lipid raft fractionation, dominant-negative CAP co-transfection, cortical actin imaging, glucose transport assays The Journal of biological chemistry High 11821390

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature 458 11309621
2001 Lipid raft microdomain compartmentalization of TC10 is required for insulin signaling and GLUT4 translocation. The Journal of cell biology 140 11502760
2003 Skeletal muscle cells and adipocytes differ in their reliance on TC10 and Rac for insulin-induced actin remodeling. Molecular endocrinology (Baltimore, Md.) 132 14615606
1998 Distinct cellular effects and interactions of the Rho-family GTPase TC10. Current biology : CB 126 9799731
2003 Insulin induces phosphatidylinositol-3-phosphate formation through TC10 activation. The EMBO journal 124 12912916
1999 The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins. Molecular and cellular biology 112 10490598
2000 Characterization of TCL, a new GTPase of the rho family related to TC10 andCcdc42. The Journal of biological chemistry 102 10967094
2014 RNA editing in RHOQ promotes invasion potential in colorectal cancer. The Journal of experimental medicine 100 24663214
2009 The TC10-Exo70 complex is essential for membrane expansion and axonal specification in developing neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 93 19846717
2001 PIST: a novel PDZ/coiled-coil domain binding partner for the rho-family GTPase TC10. Biochemical and biophysical research communications 79 11162552
2002 Small GTP-binding protein TC10 differentially regulates two distinct populations of filamentous actin in 3T3L1 adipocytes. Molecular biology of the cell 78 12134073
2002 The TC10-interacting protein CIP4/2 is required for insulin-stimulated Glut4 translocation in 3T3L1 adipocytes. Proceedings of the National Academy of Sciences of the United States of America 78 12242347
2004 Atypical protein kinase C (PKCzeta/lambda) is a convergent downstream target of the insulin-stimulated phosphatidylinositol 3-kinase and TC10 signaling pathways. The Journal of cell biology 76 14734537
2005 RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory ganglia, and corticospinal tract neurons and long-lasting specific changes following spinal cord injury. The Journal of comparative neurology 75 15736231
1999 Cellular functions of TC10, a Rho family GTPase: regulation of morphology, signal transduction and cell growth. Oncogene 70 10445846
2000 The small GTP-binding protein TC10 promotes nerve elongation in neuronal cells, and its expression is induced during nerve regeneration in rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 10818149
2013 GTP hydrolysis of TC10 promotes neurite outgrowth through exocytic fusion of Rab11- and L1-containing vesicles by releasing exocyst component Exo70. PloS one 45 24223996
2014 Local translation of TC10 is required for membrane expansion during axon outgrowth. Nature communications 43 24667291
2002 Cloning and functional characterization of related TC10 isoforms, a subfamily of Rho proteins involved in insulin-stimulated glucose transport. The Journal of biological chemistry 43 11821390
2013 Collybistin activation by GTP-TC10 enhances postsynaptic gephyrin clustering and hippocampal GABAergic neurotransmission. Proceedings of the National Academy of Sciences of the United States of America 38 24297911
2003 The exocytotic trafficking of TC10 occurs through both classical and nonclassical secretory transport pathways in 3T3L1 adipocytes. Molecular and cellular biology 37 12529401
2008 CDK5-dependent phosphorylation of the Rho family GTPase TC10(alpha) regulates insulin-stimulated GLUT4 translocation. The Journal of biological chemistry 35 18948252
2007 An NGF-induced Exo70-TC10 complex locally antagonises Cdc42-mediated activation of N-WASP to modulate neurite outgrowth. Journal of cell science 34 17635999
2018 The guanine nucleotide exchange factor Arhgef7/βPix promotes axon formation upstream of TC10. Scientific reports 30 29891904
2008 High-fat diet alters PP2A, TC10, and CIP4 expression in visceral adipose tissue of rats. Obesity (Silver Spring, Md.) 28 18388891
2005 Decreased insulin-dependent glucose transport by chronic ethanol feeding is associated with dysregulation of the Cbl/TC10 pathway in rat adipocytes. American journal of physiology. Endocrinology and metabolism 28 16105861
2002 A Crk-II/TC10 signaling pathway is required for osmotic shock-stimulated glucose transport. The Journal of biological chemistry 27 12215429
2003 Lipid Raft targeting of the TC10 amino terminal domain is responsible for disruption of adipocyte cortical actin. Molecular biology of the cell 26 12972548
2020 RHOQ is induced by DLL4 and regulates angiogenesis by determining the intracellular route of the Notch intracellular domain. Angiogenesis 23 32506201
2009 TC10 controls human myofibril organization and is activated by the sarcomeric RhoGEF obscurin. Journal of cell science 23 19258391
2001 Signaling mediated by the closely related mammalian Rho family GTPases TC10 and Cdc42 suggests distinct functional pathways. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 23 11306516
2006 TC10 and insulin-stimulated glucose transport. Methods in enzymology 22 16472699
2021 Activation of TC10-Like Transcription by Lysine Demethylase KDM4B in Colorectal Cancer Cells. Frontiers in cell and developmental biology 18 34249900
2017 The Small Rho GTPase TC10 Modulates B Cell Immune Responses. Journal of immunology (Baltimore, Md. : 1950) 18 28747344
2013 Fibronectin-induced VEGF receptor and calcium channel transactivation stimulate GLUT-1 synthesis and trafficking through PPARγ and TC10 in mouse embryonic stem cells. Stem cell research 14 23455393
2022 Knockdown of RhoQ, a member of Rho GTPase, accelerates TGF-β-induced EMT in human lung adenocarcinoma. Biochemistry and biophysics reports 12 36120491
2021 TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia. Communications biology 9 34531530
2012 TC10 is regulated by caveolin in 3T3-L1 adipocytes. PloS one 9 22900022
2010 TC10-like/TC10betaLong regulates adipogenesis by controlling mitotic clonal expansion. Biological & pharmaceutical bulletin 9 20190400
2020 Reelin activates the small GTPase TC10 and VAMP7 to promote neurite outgrowth and regeneration of dorsal root ganglia (DRG) neurons. Journal of neuroscience research 8 32652719
2008 Activation of atypical protein kinase Czeta toward TC10 is regulated by high-fat diet and aerobic exercise in skeletal muscle. Metabolism: clinical and experimental 6 18702941
2006 The activation of TC10, a Rho small GTPase, contributes to v-Rel-mediated transformation. Oncogene 4 17016434
2025 TC10 on endosomes regulates the local balance between microtubule stability and dynamics through the PAK2-JNK pathway and promotes axon outgrowth. Journal of cell science 3 40008675
2022 Differential modulation of collybistin conformational dynamics by the closely related GTPases Cdc42 and TC10. Frontiers in synaptic neuroscience 3 35989712
2017 cAMP-induced activation of protein kinase A and p190B RhoGAP mediates down-regulation of TC10 activity at the plasma membrane and neurite outgrowth. Genes to cells : devoted to molecular & cellular mechanisms 3 29072354
2025 Medium-chain triglycerides tricaprin TC10 and tricaprylin TC8 attenuated HFD-induced cognitive decline in a manner dependent on or independent of GLP-1. Scientific reports 2 40140693
2026 Nebivolol Inhibits Hepatocellular Carcinoma via RHOQ and Enhances the Efficacy of Lenvatinib. International journal of biological sciences 0 42003931
2024 TC10 differently controls the dynamics of Exo70 in growth cones of cortical and hippocampal neurons. Biophysical reports 0 39521348