| First Author | Wurtzel JG | Year | 2015 |
| Journal | Biochem Biophys Res Commun | Volume | 467 |
| Issue | 4 | Pages | 785-91 |
| PubMed ID | 26498519 | Mgi Jnum | J:318352 |
| Mgi Id | MGI:6859321 | Doi | 10.1016/j.bbrc.2015.10.064 |
| Citation | Wurtzel JG, et al. (2015) RLIP76 regulates Arf6-dependent cell spreading and migration by linking ARNO with activated R-Ras at recycling endosomes. Biochem Biophys Res Commun 467(4):785-91 |
| abstractText | R-Ras small GTPase enhances cell spreading and motility via RalBP1/RLIP76, an R-Ras effector that links GTP-R-Ras to activation of Arf6 and Rac1 GTPases. Here, we report that RLIP76 performs these functions by binding cytohesin-2/ARNO, an Arf GTPase guanine exchange factor, and connecting it to R-Ras at recycling endosomes. RLIP76 formed a complex with R-Ras and ARNO by binding ARNO via its N-terminus (residues 1-180) and R-Ras via residues 180-192. This complex was present in Rab11-positive recycling endosomes and the presence of ARNO in recycling endosomes required RLIP76, and was not supported by RLIP76(Delta1-180) or RLIP76(Delta180-192). Spreading and migration required RLIP76(1-180), and RLIP76(Delta1-180) blocked ARNO recruitment to recycling endosomes, and spreading. Arf6 activation with an ArfGAP inhibitor overcame the spreading defects in RLIP76-depleted cells or cells expressing RLIP76(Delta1-180). Similarly, RLIP76(Delta1-180) or RLIP76(Delta180-192) suppressed Arf6 activation. Together these results demonstrate that RLIP76 acts as a scaffold at recycling endosomes by binding activated R-Ras, recruiting ARNO to activate Arf6, thereby contributing to cell spreading and migration. |
