Interplay between Rab35 and Arf6 controls cargo recycling to coordinate cell adhesion and migration.
J Cell Sci
; 126(Pt 3): 722-31, 2013 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-23264734
ABSTRACT
Cells inversely adjust the plasma membrane levels of integrins and cadherins during cell migration and cell-cell adhesion but the regulatory mechanisms that coordinate these trafficking events remain unknown. Here, we demonstrate that the small GTPase Rab35 maintains cadherins at the cell surface to promote cell-cell adhesion. Simultaneously, Rab35 supresses the activity of the GTPase Arf6 to downregulate an Arf6-dependent recycling pathway for ß1-integrin and EGF receptors, resulting in inhibition of cell migration and attenuation of signaling downstream of these receptors. Importantly, the phenotypes of decreased cell adhesion and increased cell migration observed following Rab35 knock down are consistent with the epithelial-mesenchymal transition, a feature of invasive cancer cells, and we show that Rab35 expression is suppressed in a subset of cancers characterized by Arf6 hyperactivity. Our data thus identify a key molecular mechanism that efficiently coordinates the inverse intracellular sorting and cell surface levels of cadherin and integrin receptors for cell migration and differentiation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Ribosilação do ADP
/
Proteínas rab de Ligação ao GTP
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Canadá