Disease relevance of RHOQ

• Regulation of cystic fibrosis transmembrane regulator trafficking and protein expression by a Rho family small GTPase TC10 [1].

High impact information on RHOQ

• Thus, TCGAP may act as a downstream effector of TC10 in the regulation of insulin-stimulated glucose transport [2].
• Although RhoB localized to the plasma membrane (PM), Golgi, and motile peri-Golgi vesicles, TC10 localized to PMs and endosomes [3].
• Inhibition of palmitoylation mislocalized H-Ras, RhoB, and TC10 to the endoplasmic reticulum [3].
• The TC10-interacting protein CIP4/2 is required for insulin-stimulated Glut4 translocation in 3T3L1 adipocytes [4].
• Surprisingly, inhibition of Golgi membrane transport with brefeldin A did not prevent plasma membrane localization of TC10 or H-Ras [5].

Biological context of RHOQ

• It can be concluded that although TC10 expression is lower in developing and mature motor neurons compared with other Rho family members, TC10 expression is induced by nerve injury to play a crucial role in nerve regeneration, particularly neurite elongation, in cooperation with other family members [6].
• To examine the structural determinants necessary for TC10 trafficking, localization, and function in adipocytes, we generated a series of point mutations in the carboxyl-terminal targeting domain of TC10 [5].
• We demonstrate that an intact effector domain and carboxyl terminal prenylation signal are required for proper TC10 function and that TC10 signals to at least two separable downstream target pathways [7].
• In addition, TC10 interacted with the actin-binding and filament-forming protein, profilin, in both a two-hybrid cDNA library screen, and an in vitro binding assay [7].
• The small Ras-related GTPase, TC10, has been classified on the basis of sequence homology to be a member of the Rho family [7].

Anatomical context of RHOQ

• The effect of TC10 is independent of the level of CFTR expression, because a similar effect was observed in a stable cell line that expresses one-tenth of CFTR [1].
• Despite its overall similarity to TC10 and Cdc42, the constitutively active TCL mutant displays distinct morphogenic activity in REF-52 fibroblasts, producing large and dynamic F-actin-rich ruffles on the dorsal cell membrane [8].
• TC10 mRNA expression was very low in normal motor neurons; however, axotomy induced its expression dramatically [6].
• Cultured dorsal root ganglia exhibited dramatic neurite extension secondary to adenovirus-mediated expression of TC10 [6].
• These data demonstrate that TC10 and H-Ras can both traffic to the plasma membrane by at least two distinct transport mechanisms in adipocytes, one dependent upon intracellular membrane transport and another independent of the classical secretory membrane system [5].

Associations of RHOQ with chemical compounds

• We show the inhibitory TC10 (T31N) mutant, which abrogates insulin-stimulated GLUT4 translocation and glucose transport, also inhibits both cortical localization of N-WASP and F-actin formation in response to insulin [9].
• Furthermore, TC10 directly bound to Golgi COPI coat proteins through a dilysine motif in the carboxyl terminal domain consistent with a role for TC10 regulating actin polymerization on membrane transport vesicles [10].

Physical interactions of RHOQ

• Here, we report that a Rho family small GTPase TC10 interacts with CAL [1].
• We report here the identification of the TC10-interacting protein CIP4/2 (Cdc42-interacting protein 4/2) as an effector in this pathway [4].
• These results suggest that the TC10/exocyst complex/SAP97 axis plays an important role in the tethering of Glut4 vesicles to the plasma membrane in adipocytes [11].
• TC10 binds directly to obscurin via its predicted RhoGEF motif [12].

Regulatory relationships of RHOQ

• These data suggest that CIP4/2 may play an important role in insulin-stimulated glucose transport as a downstream effector of TC10 [4].
• In support of this model, a GTPase-deficient TC10 mutant potently inhibited EGF-induced vesicular fusion in HeLa cells and depolarization-induced neuronal secretion [13].
• Furthermore, we found that GTP hydrolysis by TC10 in the vicinity of the plasma membrane was dependent on Rac and the redox-regulated Rho GAP, p190RhoGAP-A [13].

Other interactions of RHOQ

• Metabolic pulse-chase experiments show that TC10 did not affect CFTR maturation, suggesting that it exerts its effects on the mature CFTR [1].
• On the other hand, replacement of the corresponding region of TC10 with the AB region enabled TC10 to acquire ACK-binding ability [14].
• Overexpression of mutant forms of CIP4/2 containing an N-terminal deletion or with diminished TC10 binding inhibits insulin-stimulated Glut4 translocation [4].
• The Borg (binder of Rho GTPases) family proteins interact with CDC42 and TC10 in a guanosine triphosphate (GTP)-dependent manner [15].
• In the present study, we raised the possibility that Rhotekin interacts with a PDZ-protein, PIST (PDZ domain protein interacting specifically with TC10) in vitro, and found that these proteins form complex in the rat brain tissues [16].

References