Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex.
Curr Biol
; 11(21): 1645-55, 2001 Oct 30.
Article
em En
| MEDLINE
| ID: mdl-11696321
ABSTRACT
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 IRSp53Mena complex initiates actin filament assembly into filopodia.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Pseudópodes
/
Proteínas de Transporte
/
Proteína cdc42 de Ligação ao GTP
/
Proteínas do Citoesqueleto
/
Proteínas do Tecido Nervoso
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article