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Active Arf6 Recruits ARNO/Cytohesin GEFs to the PM by Binding Their PH Domains

Authors :
Cohen, Lee Ann
Honda, Akira
Varnai, Peter
Brown, Fraser D.
Balla, Tamas
Donaldson, Julie G.
Source :
Molecular Biology of the Cell; June 2007, Vol. 18 Issue: 6 p2244-2253, 10p
Publication Year :
2007

Abstract

ARNO is a soluble guanine nucleotide exchange factor (GEF) for the Arf family of GTPases. Although in biochemical assays ARNO prefers Arf1 over Arf6 as a substrate, its localization in cells at the plasma membrane (PM) suggests an interaction with Arf6. In this study, we found that ARNO activated Arf1 in HeLa and COS-7 cells resulting in the recruitment of Arf1 on to dynamic PM ruffles. By contrast, Arf6 was activated less by ARNO than EFA6, a canonical Arf6 GEF. Remarkably, Arf6 in its GTP-bound form recruited ARNO to the PM and the two proteins could be immunoprecipitated. ARNO binding to Arf6 was not mediated through the catalytic Sec7 domain, but via the pleckstrin homology (PH) domain. Active Arf6 also bound the PH domain of Grp1, another ARNO family member. This interaction was direct and required both inositol phospholipids and GTP. We propose a model of sequential Arf activation at the PM whereby Arf6-GTP recruits ARNO family GEFs for further activation of other Arf isoforms.

Details

Language :
English
ISSN :
10591524 and 19394586
Volume :
18
Issue :
6
Database :
Supplemental Index
Journal :
Molecular Biology of the Cell
Publication Type :
Periodical
Accession number :
ejs46605160
Full Text :
https://doi.org/10.1091/mbc.e06-11-0998