Affinage

Showing RHOQ — TC10 is a alias.

RHOQ

Rho-related GTP-binding protein RhoQ · UniProt P17081

Length
205 aa
Mass
22.7 kDa
Annotated
2026-06-10
48 papers in source corpus 31 papers cited in narrative 31 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

RHOQ (TC10) is a Rho-family GTPase that couples membrane trafficking to actin and microtubule remodeling at specialized membrane microdomains, governing insulin-stimulated glucose uptake, polarized membrane expansion in neurons, myofibril assembly, and cancer cell invasion (PMID:11309621, PMID:19846717, PMID:19258391). It localizes to caveolin-enriched lipid rafts through processing in the secretory membrane system and C-terminal cysteine modification, where Caveolin 1 binds its GDP-bound form to hold it inactive until stimulation (PMID:11502760, PMID:12529401, PMID:22900022). In adipocytes, insulin activates TC10 in parallel with—and independent of—PI3K via a CAP/Cbl/CrkII-C3G cascade at rafts, driving PtdIns-3-P production, CIP4/2 recruitment, and Par6/Par3/PKCζ assembly to promote GLUT4 translocation, with its N-terminal extension required for cortical actin remodeling and CDK5 phosphorylation of Thr197 maintaining raft residence (PMID:11309621, PMID:12912916, PMID:12242347, PMID:14734537, PMID:12972548, PMID:18948252). As an active GTPase TC10 engages effectors shared with Cdc42 and Rac, including PAK and JNK kinases and N-WASP, and binds the exocyst component Exo70 to tether secretory vesicles (PMID:9799731, PMID:12134073, PMID:19846717). In neurons, locally translated TC10 on Rab11-positive recycling endosomes drives stimulus-evoked membrane expansion and axon outgrowth: GTP hydrolysis releases Exo70 to accelerate vesicle fusion, while a PAK2-JNK pathway phosphorylates the microtubule regulators SCG10 and MAP1B (PMID:24223996, PMID:24667291, PMID:40008675). TC10 also activates the GEF collybistin by relieving its SH3-domain autoinhibition to promote gephyrin clustering at inhibitory synapses, is loaded by the muscle GEF obscurin during myofibril assembly, and at invadopodia controls MT1-MMP surface exposure and matrix degradation via p190RhoGAP and Exo70 (PMID:24297911, PMID:35989712, PMID:19258391, PMID:34531530).

Mechanistic history

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

    Establishing TC10 as a functional GTPase required defining its enzymatic properties and effector repertoire relative to Cdc42 and Rac.

    Evidence Two-hybrid screen, GST pulldowns, in vitro GTPase and kinase assays mapping an effector panel

    PMID:9799731

    Open questions at the time
    • Cellular context of effector engagement not defined
    • Did not establish physiological upstream activators
  2. 1999 Medium

    Cellular consequences of TC10 activation were mapped to filopodia, JNK/transcriptional signaling, and oncogenic transformation, plus a GTP-dependent Borg/CRIB effector class, framing TC10 as a Cdc42-like signaling node.

    Evidence Constitutively active/dominant-negative mutants, luciferase reporters, focus formation assay, two-hybrid screen with CRIB-domain mapping

    PMID:10445846 PMID:10490598

    Open questions at the time
    • Transformation assayed in overexpression context
    • Physiological relevance of Borg binding untested
  3. 2001 High

    TC10 was placed in the insulin-signaling network as a PI3K-independent driver of GLUT4 translocation activated by the CAP/Cbl/CrkII-C3G cascade specifically at lipid rafts.

    Evidence Dominant-negative epistasis, raft/non-raft chimeras, dominant-negative caveolin, subcellular fractionation and GLUT4 translocation in adipocytes

    PMID:11309621 PMID:11502760

    Open questions at the time
    • Direct GEF for insulin-stimulated activation not identified here
    • Effectors downstream of activated TC10 not yet defined
  4. 2002 High

    Downstream effectors and isoform/stimulus specificity of TC10 in glucose transport were defined, linking TC10 to CIP4/2 recruitment, N-WASP-dependent actin, COPI/secretory trafficking, and osmotic-shock GLUT4 mobilization.

    Evidence Co-IP, TC10 epistasis over CIP4/2 localization, in vitro actin polymerization in Xenopus extracts, COPI binding, isoform comparison and pharmacological dissection

    PMID:11821390 PMID:12134073 PMID:12215429 PMID:12242347

    Open questions at the time
    • Quantitative contribution of each effector to GLUT4 vesicle docking unresolved
    • Direct versus indirect actin effects not fully separated
  5. 2003 High

    The lipid-raft determinants and a lipid second messenger were defined, showing the N-terminal extension targets rafts and drives cortical actin disruption while raft-localized TC10 generates GLUT4-mobilizing PtdIns-3-P.

    Evidence Chimeric/truncation/point mutants of the N-terminal extension, C206S/C209S cysteine mutants, BFA/temperature blocks, lipid mass spectrometry and FYVE probes

    PMID:11502760 PMID:12529401 PMID:12912916 PMID:12972548

    Open questions at the time
    • Enzyme producing PtdIns-3-P downstream of TC10 not identified
    • Mechanism linking N-terminal raft targeting to actin disruption undefined
  6. 2004 High

    TC10 was shown to assemble a PI3K-independent polarity-kinase module, recruiting Par6/Par3 and activating PKCζ/λ to feed into GSK-3β regulation.

    Evidence Multi-protein Co-IP, dominant mutants, PI3K inhibitor and cholesterol depletion, PKCζ phosphorylation assays

    PMID:14734537

    Open questions at the time
    • Direct versus indirect PKCζ activation mechanism unresolved
    • Physiological output of GSK-3β phosphorylation not quantified
  7. 2008 High

    A regulatory phosphorylation was identified showing CDK5 modifies TC10 at Thr197 to sustain raft localization and insulin-responsive GTP loading.

    Evidence CDK5 siRNA/inhibitor, phospho-specific IP, T197A/T197D mutants, fractionation, GTP-loading and GLUT4 assays

    PMID:18948252

    Open questions at the time
    • Phosphatase reversing T197 not identified
    • Mechanism by which T197 phosphorylation maintains raft residence unclear
  8. 2009 High

    TC10's role in polarized exocytosis and tissue morphogenesis was established through its Exo70 partnership in axon growth and its dedicated muscle GEF obscurin in myofibril assembly.

    Evidence Reciprocal Co-IP, siRNA/shRNA, dominant mutants, live membrane imaging in neurons; in vitro GEF and binding assays plus loss-of-function in primary myoblasts

    PMID:19258391 PMID:19846717

    Open questions at the time
    • GEFs for TC10 in non-muscle insulin signaling still unidentified
    • Structural basis of obscurin-TC10 specificity undefined
  9. 2012 Medium

    The inactive-state control of TC10 was clarified by showing Caveolin 1 binds GDP-TC10 and stabilizes it, restraining basal activity against TC10's intrinsically rapid nucleotide exchange.

    Evidence GDP/GTP-state-specific Co-IP, in vitro exchange kinetics, Caveolin 1 knockdown with activity readout

    PMID:22900022

    Open questions at the time
    • Single-lab Co-IP without structural confirmation
    • How insulin displaces caveolin to permit activation unresolved
  10. 2013 Medium

    TC10 was defined as an upstream activator of collybistin at inhibitory synapses and shown to switch GTP-hydrolysis-dependent control of Exo70 release during neurite outgrowth.

    Evidence Co-IP with PH-domain specificity, mIPSC recordings, gephyrin cluster imaging; FRET activity biosensor with vesicle tracking and rescue tests

    PMID:24223996 PMID:24297911

    Open questions at the time
    • GEF activating TC10 at the synapse not identified
    • Coupling of vesicular GTP hydrolysis to fusion machinery not structurally defined
  11. 2014 High

    TC10's spatial regulation was extended to mRNA localization (local axonal translation driving membrane expansion) and to disease via RNA editing producing a hyperactive N136S variant that enhances cancer cell invasion.

    Evidence Axon-specific knockdown, local translation reporters, mTOR/PI3K inhibitors; transcriptome sequencing, edited-protein expression, GTPase and invasion assays

    PMID:24663214 PMID:24667291

    Open questions at the time
    • Trans-acting factors localizing TC10 mRNA undefined
    • In vivo tumor relevance of N136S editing not established
  12. 2017 Medium

    Spatial inactivation of TC10 at the plasma membrane was mapped to a cAMP-PKA-STEF-Rac1-p190B RhoGAP circuit required for cAMP-induced neurite outgrowth.

    Evidence FRET TC10 biosensor, PKA inhibitor, p190A/B and STEF siRNA, Rac1-N17 expression, neurite outgrowth assay

    PMID:29072354

    Open questions at the time
    • Direct GAP-substrate engagement not biochemically reconstituted
    • Single-lab FRET-based epistasis
  13. 2018 Medium

    An upstream GEF and Cdc42-independent axon pathway were defined, with Arhgef7 (βPix) acting through TC10 to drive cortical axon formation.

    Evidence In utero electroporation knockdown, rescue by active TC10, Co-IP, Cdc42 epistasis

    PMID:29891904

    Open questions at the time
    • Direct GEF activity of Arhgef7 toward TC10 not enzymatically demonstrated
    • Single Co-IP for the interaction
  14. 2020 Medium

    TC10's roles broadened to receptor trafficking control, stabilizing Notch1 against lysosomal degradation in a DLL4/Notch feed-forward loop during angiogenesis.

    Evidence siRNA/overexpression in endothelial cells, sprouting and in vivo angiogenesis assays, NICD fractionation, autophagy/lysosome inhibitor experiments

    PMID:32506201

    Open questions at the time
    • Mechanism by which TC10 diverts Notch1 from degradation unknown
    • Direct TC10-Notch interaction not shown
  15. 2021 Medium

    TC10 was shown to control cancer invadopodia function by regulating MT1-MMP surface exposure and ECM degradation through p190RhoGAP and Exo70.

    Evidence FRET TC10 biosensor at invadopodia, knockdown, p190RhoGAP modulation, MT1-MMP surface and ECM degradation assays

    PMID:34531530

    Open questions at the time
    • GEF activating TC10 at invadopodia unidentified
    • Single-lab biosensor study
  16. 2025 Medium

    The microtubule arm of TC10's outgrowth function was defined, linking endosomal TC10 to a PAK2-JNK pathway phosphorylating SCG10 and MAP1B.

    Evidence TC10-knockout neurons, phosphoproteomics, PAK2 autophosphorylation, endosomal fractionation, PAK inhibitor, axon retraction assay

    PMID:40008675

    Open questions at the time
    • Direct PAK2 activation by TC10 versus scaffold role unresolved
    • Integration with the Exo70/exocytosis arm on the same endosomes undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TC10 nucleotide cycling is coordinated across distinct compartments (rafts, recycling endosomes, invadopodia) and which GEFs and GAPs act in each context remain incompletely defined.
  • No unified model linking compartment-specific GEF/GAP control to effector choice
  • Structural basis of TC10 effector and regulator selectivity unresolved
  • In vivo physiological and disease roles of most pathways untested in animal models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 4 GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3
Partners
ARHGEF7ARHGEF9CAV1EXOC7GOPCOBSCNPARD6ATRIP10
Complex memberships
exocyst

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Insulin-stimulated GLUT4 translocation requires TC10 activation via a CAP/Cbl/CrkII-C3G signaling cascade at lipid rafts, operating in parallel with PI3K and independent of PI3K activity. Phosphorylated Cbl recruits the CrkII-C3G complex to lipid rafts where C3G activates TC10. Dominant-negative mutant expression, subcellular fractionation, GTP-loading assays, GLUT4 translocation assays in 3T3-L1 adipocytes Nature High 11309621
2001 TC10 localizes to caveolin-enriched lipid raft microdomains via processing through the secretory membrane trafficking system, and lipid raft compartmentalization is required for insulin-induced TC10 activation and its inhibitory effect on GLUT4 translocation. TC10 chimeras directed to non-raft domains (via K-Ras targeting) were not activated by insulin and did not inhibit GLUT4 translocation. TC10/H-Ras and TC10/K-Ras chimeras, dominant-interfering caveolin-3 mutant (Cav3/DGV) expression, sucrose density gradient fractionation, GLUT4 translocation assays The Journal of cell biology High 11502760
1998 TC10 GTPase stimulates JNK and PAK activities and interacts with a set of effectors overlapping with Cdc42 and Rac (αPAK, βPAK, γPAK, MRCKα/β, MLK2, N-WASP, MSE55) but does not interact with MLK3, WASP, or ACK-1 and interacts only weakly with ACK-1. TC10 has lower intrinsic GTPase activity than Cdc42 and greater responsiveness to p50RhoGAP. Two-hybrid screen, GST pulldown assays, in vitro GTPase activity assays, JNK and PAK kinase activity assays Current biology : CB High 9799731
2003 Insulin specifically induces formation of phosphatidylinositol-3-phosphate (PtdIns-3-P) through TC10 activation at lipid rafts, and exogenous PtdIns-3-P is sufficient to induce GLUT4 translocation to the plasma membrane. Lipid mass spectrometry, PtdIns-3-P detection with FYVE domain probes, dominant-active/negative TC10 mutants, exogenous lipid addition, GLUT4 translocation assays The EMBO journal Medium 12912916
1999 The Borg family of proteins (Borg1, 2, 4, 5) binds TC10 in a GTP-dependent manner via an intact CRIB domain; Borg3 does not bind TC10. No interaction was detected between Borgs and Rac1 or RhoA. Two-hybrid screen, GST pulldown assays, CRIB domain deletion mutants Molecular and cellular biology Medium 10490598
2009 TC10 interacts with the exocyst component Exo70 in neurons; IGF-1 activates TC10, which triggers translocation of Exo70 to the plasma membrane at the distal axon and growth cone. TC10 and Exo70 function are required for membrane addition and axon elongation, and for polarized insertion of the IGF-1 receptor to specify the axon. Co-immunoprecipitation, dominant-negative/constitutively active TC10 mutant expression, siRNA knockdown of TC10 and Exo70, live imaging of membrane expansion in hippocampal neurons and isolated growth cones The Journal of neuroscience High 19846717
2001 PIST (a PDZ/coiled-coil domain protein) specifically interacts with TC10:GTP (but not GDP-bound TC10) via a leucine zipper-containing coiled-coil domain. Mutation of the TC10 effector binding domain disrupts this interaction. PIST does not interact detectably with Cdc42 and forms homodimers. Two-hybrid screen, GST pulldown assays, point and deletion mutagenesis, co-immunoprecipitation Biochemical and biophysical research communications Medium 11162552
2002 Constitutively active TC10 (Q75L) induces actin comet tails in Xenopus oocyte extracts and perinuclear actin polymerization in 3T3-L1 adipocytes via an N-WASP-dependent mechanism, while also disrupting cortical actin via the N-terminal extension (amino acids 1–79). TC10 directly binds Golgi COPI coat proteins through a dilysine motif in its C-terminal domain. Disruption of perinuclear actin by TC10 or N-WASP/ΔVCA reduces VSV-G trafficking to the plasma membrane. In vitro actin polymerization assay (Xenopus oocyte extracts), TC10 deletion mutants, COPI binding assay, VSV-G trafficking assay in adipocytes, fluorescence microscopy Molecular biology of the cell High 12134073
2002 CIP4/2 (Cdc42-interacting protein 4/2) is a TC10 effector required for insulin-stimulated GLUT4 translocation. CIP4/2 translocates from an intracellular compartment to the plasma membrane upon insulin stimulation; this translocation is prevented by dominant-negative TC10 and promoted by constitutively active TC10. N-terminal deletion mutants of CIP4/2 or reduced TC10-binding mutants inhibit insulin-stimulated Glut4 translocation. Co-immunoprecipitation, subcellular localization by fluorescence microscopy, constitutively active and dominant-negative TC10 expression, CIP4/2 mutant overexpression, GLUT4 translocation assay Proceedings of the National Academy of Sciences of the United States of America High 12242347
2004 Constitutively active TC10 (Q75L) recruits PKCζ/λ to plasma membrane lipid raft microdomains through an indirect association with the Par6-Par3 complex; this recruitment is insensitive to PI3K inhibition. TC10 also promotes activation-loop phosphorylation of PKCζ. TC10-activated PKCζ/λ contributes to GSK-3β phosphorylation independently of PI3K-PKB. Subcellular fractionation, co-immunoprecipitation (TC10-Par6-Par3-PKCζ), constitutively active and dominant-negative TC10 mutants, PI3K inhibitor treatment, Clostridium difficile toxin B, cholesterol depletion, PKCζ phosphorylation assay The Journal of cell biology High 14734537
2003 Lipid raft targeting of the TC10α N-terminal extension (amino acids 1–16 sufficient) is responsible for disruption of adipocyte cortical actin and inhibition of insulin-stimulated GLUT4 translocation. The N-terminal extension fused to H-Ras (raft-targeted) disrupts cortical actin; the same extension fused to K-Ras (non-raft) does not. GAG and GPG sequences within the N-terminal extension are required for these effects. TC10α/H-Ras and TC10α/K-Ras chimeric constructs with progressive truncations, point mutations of GAG/GPG motifs, cortical actin imaging, GLUT4 translocation assay Molecular biology of the cell High 12972548
2003 TC10 localizes to caveolin-positive lipid raft microdomains via the secretory membrane system (C209S mutation excludes TC10 from both). TC10 can also traffic to the plasma membrane independently of the classical secretory pathway (brefeldin A and 19°C block do not prevent plasma membrane localization). C206S mutation does not alter raft localization. TC10 point mutants (C206S, C209S, double mutant), brefeldin A treatment, 19°C temperature block, sucrose density fractionation, fluorescence microscopy Molecular and cellular biology Medium 12529401
2008 CDK5 phosphorylates TC10α on threonine 197 (T197) in lipid raft domains, dependent on Fyn-mediated CDK5 activation. T197A mutation excludes TC10α from lipid rafts and prevents its GTP-loading by insulin; T197D (phosphomimetic) is lipid-raft localized and is GTP-loaded by insulin. CDK5-dependent phosphorylation of TC10α disrupts cortical actin and inhibits insulin-stimulated GLUT4 translocation. CDK5 siRNA knockdown, CDK5 inhibitor olomoucine, phospho-specific immunoprecipitation, T197A and T197D TC10α mutants, sucrose density fractionation, GTP loading assay, GLUT4 translocation assay The Journal of biological chemistry High 18948252
1999 Constitutively active TC10 (Q75L) stimulates filopodia formation, JNK activation, SRF-dependent transcription, NF-κB-dependent transcription, and synergizes with activated Raf to transform NIH3T3 cells. TC10 requires an intact effector domain and C-terminal prenylation for function. Wild-type TC10 is required for full H-Ras transforming potential. TC10 interacts with profilin in two-hybrid and in vitro binding assays. Constitutively active and dominant-negative TC10 mutant expression, luciferase reporter assays (SRF, NF-κB), JNK kinase assay, focus formation assay, two-hybrid screen, in vitro binding assay Oncogene Medium 10445846
2009 Obscurin, a sarcomere-associated protein, acts as a specific GEF (guanine nucleotide exchange factor) for TC10 but not for Rac or Cdc42. TC10 binds directly to obscurin's RhoGEF motif. TC10 activity is required for myofibril assembly in human primary skeletal myoblasts; inhibition by dominant-negative TC10 or shRNA knockdown blocks myofibril formation. Direct binding assay (TC10-obscurin), GEF activity assay (nucleotide exchange), GST pulldown, dominant-negative TC10 mutant expression, shRNA knockdown, immunofluorescence of myofibril assembly Journal of cell science High 19258391
2013 GTP-bound TC10 binds to the pleckstrin homology (PH) domain of collybistin and activates it by relieving its autoinhibition (mediated by the SH3 domain). This TC10-collybistin interaction stimulates gephyrin clustering at inhibitory synapses and increases miniature inhibitory postsynaptic current amplitudes; dominant-negative TC10 reduces these effects. This activation does not require collybistin's GEF activity. Co-immunoprecipitation, constitutively active and dominant-negative TC10 in neurons, mIPSC recordings, immunofluorescence of gephyrin cluster density Proceedings of the National Academy of Sciences of the United States of America High 24297911
2013 GTP hydrolysis of TC10 (rather than GTP-bound TC10) promotes neurite outgrowth by releasing Exo70 to accelerate vesicle fusion. TC10 activity is higher on vesicles than at the plasma membrane; TC10-positive vesicles fuse to the plasma membrane in NGF-treated cells. TC10 resides on Rab11- and L1-containing vesicles, and these vesicle populations are involved in TC10-mediated exocytosis. Constitutively active TC10 cannot rescue TC10-depletion-induced reduction in neurite outgrowth. FRET-based TC10 activity biosensor in live neurons/PC12 cells, TC10 knockdown, colocalization analysis (Rab11, L1, Exo70), live imaging of vesicle fusion PloS one Medium 24223996
2014 Local (intra-axonal) translation of TC10 mRNA is required for stimulus-induced membrane expansion and axon outgrowth in DRG axons. Axon-specific knockdown of TC10 mRNA inhibits membrane enlargement. PI3K-dependent activation of Rheb-mTOR pathway triggers simultaneous local synthesis of TC10 and Par3. Axon-specific siRNA knockdown, local translation reporters, mTOR inhibitor (rapamycin), PI3K inhibitor, mTOR pathway activation/inhibition, membrane expansion assay in DRG axons Nature communications High 24667291
2007 NGF induces an interaction between activated TC10 and Exo70 in PC12 cells (detected by FRET/FLIM). The TC10-Exo70 complex promotes membrane protrusion but locally antagonizes Cdc42-dependent activation of N-WASP, enabling a switch between Cdc42- or TC10-dominated forms of membrane outgrowth. Exo70 is responsible for targeting the TC10-Exo70 complex to sites of membrane protrusion. FRET/FLIM imaging of TC10-Exo70 interaction, N-WASP FRET activity sensor, siRNA knockdown (Cdc42, Exo70), dominant-negative and constitutively active Cdc42/TC10 constructs Journal of cell science Medium 17635999
2014 A-to-I RNA editing of RHOQ transcripts results in an N136S amino acid substitution that increases RhoQ GTPase activity, promotes actin cytoskeletal reorganization, and enhances invasion potential in colorectal cancer cells. KRAS mutation further increases invasion in the presence of RhoQ N136S. Whole-genome/transcriptome sequencing to identify editing, expression of edited vs. unedited RHOQ in cancer cell lines, GTPase activity assay, actin cytoskeleton imaging, invasion assay The Journal of experimental medicine Medium 24663214
2020 RHOQ is induced by DLL4/Notch signaling and is required for Notch intracellular domain (NICD) nuclear translocation and Notch signaling. Loss of RHOQ causes Notch1 to be targeted for lysosomal/autophagy degradation, sequestering NICD from the nucleus. RHOQ forms a feed-forward loop: DLL4/Notch induces RHOQ, which in turn promotes Notch signaling. RHOQ siRNA knockdown in endothelial cells, RHOQ overexpression, in vitro sprouting assay, in vivo angiogenesis model, subcellular fractionation/NICD localization, autophagy/lysosome inhibitor experiments Angiogenesis Medium 32506201
2018 Arhgef7 (βPix) acts upstream of TC10 to promote axon formation during cortical development. Loss of Arhgef7 causes axon loss that cannot be rescued by active Cdc42 but can be rescued by expression of active TC10. Arhgef7 interacts with TC10. In utero electroporation knockdown of Arhgef7 in cortex, rescue by active TC10, co-immunoprecipitation (Arhgef7-TC10), Cdc42 epistasis experiments Scientific reports Medium 29891904
2012 Caveolin 1 interacts with TC10 specifically in its GDP-bound (inactive) state and stabilizes GDP binding, maintaining TC10 in an inactive state in unstimulated adipocytes. Knockdown of Caveolin 1 increases basal TC10 activity. TC10 intrinsically has rapid nucleotide exchange (high magnesium decreases exchange rate). Co-immunoprecipitation, GDP/GTP exchange kinetics in vitro, Caveolin 1 siRNA knockdown, GTP-loading assay in adipocytes PloS one Medium 22900022
2002 TC10α and TC10β are two isoforms (∼70% identity) both activated by insulin through the CAP/Cbl pathway in 3T3-L1 adipocytes and both localize to lipid rafts. However, TC10α overexpression completely blocks glucose transport and disrupts cortical actin, whereas TC10β only partially inhibits glucose transport and has little effect on cortical actin. cDNA cloning, co-transfection with dominant-negative CAP, GTP-loading assay, sucrose density fractionation, actin imaging, glucose transport assay The Journal of biological chemistry Medium 11821390
2002 TC10 activation is required for osmotic shock-stimulated GLUT4 translocation and glucose transport through a Crk-II pathway, dependent on cortical actin remodeling at caveolin-enriched membrane domains, independently of PI3K and PLCγ. Dominant-interfering TC10/T31N expression, Clostridium difficile toxin B, latrunculin B, jasplakinolide, PI3K and PLCγ inhibitors, GLUT4 translocation assay The Journal of biological chemistry Medium 12215429
2021 TC10 regulates surface exposure of membrane type-1 matrix metalloproteinase (MT1-MMP) at invadopodia in breast cancer cells, controlling extracellular matrix degradation. TC10 activity at invadopodia is regulated by p190RhoGAP and involves downstream interaction with Exo70. Loss of TC10 reduces MT1-MMP plasma membrane exposure and ECM degradation. FRET TC10 biosensor at invadopodia, TC10 KD, p190RhoGAP overexpression/KD, Exo70 interaction, MT1-MMP surface exposure assay, ECM degradation assay Communications biology Medium 34531530
2025 TC10 on recycling endosomes (Rab11-positive) promotes axon outgrowth by balancing microtubule stability and dynamics through a PAK2-JNK pathway. TC10 loss reduces PAK2 autophosphorylation and PAK2 localization to Rab11-positive endosomes, decreases JNK phosphorylation, and reduces phosphorylation of the microtubule-binding proteins SCG10 and MAP1B. MKK4/MKK7 mediate signaling from TC10-activated PAK to JNK on JIP1-positive endosomes. TC10 knockout neurons, phospho-proteomics, PAK2 autophosphorylation assay, subcellular fractionation of endosomal compartments, PAK inhibitor treatment, axon retraction assay Journal of cell science Medium 40008675
2017 TC10 inactivation at the plasma membrane is mediated by a cAMP-PKA-STEF-Rac1-p190B RhoGAP pathway. cAMP treatment decreases TC10 activity locally at extending neurite tips; this inactivation requires PKA and p190B (but not p190A). TC10 depletion reduces cAMP-induced neurite outgrowth. Constitutively active TC10 cannot rescue this reduction, consistent with GTP hydrolysis being required for vesicle fusion. FRET TC10 biosensor, PKA inhibitor, p190A/B siRNA knockdown, STEF depletion, Rac1-N17 expression, neurite outgrowth assay Genes to cells Medium 29072354
2022 TC10 (RhoQ) binds to the closed/autoinhibited form of collybistin and relieves its autoinhibition (unlike Cdc42, which only interacts with collybistin when it is forced into an open conformation by destabilizing mutations). GTP-TC10 binding to collybistin drives collybistin conformational switch from closed to open state, as measured by FRET. Time-resolved fluorescence FRET sensors of collybistin conformation, TC10 and Cdc42 binding assays with wild-type and mutant collybistin Frontiers in synaptic neuroscience Medium 35989712
2024 TC10 stimulates Exo70 mobility in HeLa cells but decreases Exo70 diffusion in the growth cone of cortical neurons; TC10 overexpression does not affect Exo70 mobility in hippocampal neuron growth cones. This indicates cell-type- and compartment-specific regulation of exocyst tethering by TC10. Super-resolution microscopy (single-particle localization and tracking), mean square displacement analysis, TC10 overexpression in HeLa and cortical/hippocampal neurons Biophysical reports Low 39521348
2020 Reelin activates TC10 in DRG neurons, and this activation is mediated upstream by Cdc42 (Cdc42 controls TC10 activity). TC10 is required for axon development in DRG neurons. Reelin stimulates fusion of VAMP7-containing membrane carriers that also contain TC10 at the growth cone. TC10 activity assay (GTP-pulldown) after Reelin treatment, Cdc42 dominant-negative epistasis over TC10 activation, TC10 siRNA, VAMP7 vesicle fusion imaging Journal of neuroscience research Low 32652719

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 459 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 101 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 95 19846717
2001 PIST: a novel PDZ/coiled-coil domain binding partner for the rho-family GTPase TC10. Biochemical and biophysical research communications 80 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 77 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 46 24223996
2014 Local translation of TC10 is required for membrane expansion during axon outgrowth. Nature communications 44 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 10 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

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