RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho.
Rap1 and Rho small G proteins have been implicated in the neurite outgrowth, but the functional relationship between Rap1 and Rho in the neurite outgrowth remains to be established. Here we identified a potent Rho GTPase-activating protein (GAP), RA-RhoGAP, as a direct downstream target of Rap1 in the neurite outgrowth. RA-RhoGAP has the RA and GAP domains and showed GAP activity specific for Rho, which was enhanced by the binding of the GTP-bound active form of Rap1 to the RA domain. Overexpression of RA-RhoGAP induced inactivation of Rho for promoting the neurite outgrowth in a Rap1-dependent manner. Knockdown of RA-RhoGAP reduced the Rap1-induced neurite outgrowth. These results indicate that RA-RhoGAP transduces a signal from Rap1 to Rho and regulates the neurite outgrowth.
Yamada
Tomohiro
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Sakisaka
Toshiaki
T
Hisata
Shu
S
Baba
Takeshi
T
Takai
Yoshimi
Y
D002460:Cell Line; D049109:Cell Proliferation; D048429:Cell Size; D000242:Cyclic AMP / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry; D006801:Humans; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques; D020741:rho GTP-Binding Proteins / Q000737:chemistry*
C502036:ARHGAP20 protein, human; D020690:GTPase-Activating Proteins; D014157:Transcription Factors; C085379:rho GTPase-activating protein; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D020741:rho GTP-Binding Proteins