An essential role for ARF6-regulated membrane traffic in adherens junctionturnover and epithelial cell migration

Citation
F. Palacios et al., An essential role for ARF6-regulated membrane traffic in adherens junctionturnover and epithelial cell migration, EMBO J, 20(17), 2001, pp. 4973-4986
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
0261-4189 → ACNP
Volume
20
Issue
17
Year of publication
2001
Pages
4973 - 4986
Database
ISI
SICI code
0261-4189(20010903)20:17<4973:AERFAM>2.0.ZU;2-L
Abstract
We describe a novel role for the ARF6 GTPase in the regulation of adherens junction (AJ) turnover in MDCK epithelial cells. Expression of a GTPase-def ective ARF6 mutant, ARF6(Q67L), led to a loss of AJs and ruffling of the la teral plasma membrane via mechanisms that were mutually exclusive. ARF6-GTP -induced AJ disassembly did not require actin remodeling, but was dependent on the internalization of E-cadherin into the cytoplasm via vesicle transp ort. ARF6 activation was accompanied by increased migratory potential, and treatment of cells with hepatocyte growth factor (HGF) induced the activati on of endogenous ARF6. The effect of ARF6(Q67L) on AJs was specific since A RF6 activation did not perturb tight junction assembly or cell polarity. In contrast, dominant-negative ARF6, ARF6(T27N), localized to AJs and its exp ression blocked cell migration and HGF-induced internalization of cadherin- based junctional components into the cytoplasm. Finally, we show that ARF6 exerts its role downstream (if v-Src activation during the disassembly of A Js. These findings document an essential role for ARF6-regulated membrane t raffic in AJ disassembly and epithelial cell migration.