| First Author | Krugmann S | Year | 2001 |
| Journal | Curr Biol | Volume | 11 |
| Issue | 21 | Pages | 1645-55 |
| PubMed ID | 11696321 | Mgi Jnum | J:196124 |
| Mgi Id | MGI:5486572 | Doi | 10.1016/s0960-9822(01)00506-1 |
| Citation | Krugmann S, et al. (2001) Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex. Curr Biol 11(21):1645-55 |
| abstractText | BACKGROUND: The Rho GTPases Rho, Rac, and Cdc42 regulate the organization of the actin cytoskeleton by interacting with multiple, distinct downstream effector proteins. Cdc42 controls the formation of actin bundle-containing filopodia at the cellular periphery. The molecular mechanism for this remains as yet unclear. RESULTS: We report here that Cdc42 interacts with IRSp53/BAP2 alpha, an SH3 domain-containing scaffold protein, at a partial CRIB motif and that an N-terminal fragment of IRSp53 binds, via an intramolecular interaction, to the CRIB motif-containing central region. Overexpression of IRSp53 in fibroblasts leads to the formation of filopodia, and both this and Cdc42-induced filopodia are inhibited by expression of the N-terminal IRSp53 fragment. Using affinity chromatography, we have identified Mena, an Ena/VASP family member, as interacting with the SH3 domain of IRSp53. Mena and IRSp53 act synergistically to promote filopodia formation. CONCLUSION: We conclude that the interaction of Cdc42 with the partial CRIB motif of IRSp53 relieves an intramolecular, autoinhibitory interaction with the N terminus, allowing the recruitment of Mena to the IRSp53 SH3 domain. This IRSp53:Mena complex initiates actin filament assembly into filopodia. |
