Premium
EFA6, a sec7 domain‐containing exchange factor for ARF6, coordinates membrane recycling and actin cytoskeleton organization
Author(s) -
Franco Michel,
Peters Peter J.,
Boretto Joëlle,
van Donselaar Elly,
Neri Antonino,
D'SouzaSchorey Crislyn,
Chavrier Philippe
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.6.1480
Subject(s) - guanine nucleotide exchange factor , adp ribosylation factor , pleckstrin homology domain , biology , microbiology and biotechnology , endocytosis , cytoskeleton , endosome , actin cytoskeleton , cytoplasm , rac1 , actin , gtpase , golgi apparatus , biochemistry , receptor , cell , signal transduction , intracellular , endoplasmic reticulum
We have identified a human cDNA encoding a novel protein, exchange factor for ARF6 (EFA6), which contains Sec7 and pleckstrin homology domains. EFA6 promotes efficient guanine nucleotide exchange on ARF6 and is distinct from the ARNO family of ARF1 exchange factors. The protein localizes to a dense matrix on the cytoplasmic face of plasma membrane invaginations, induced on its expression. We show that EFA6 regulates endosomal membrane recycling and promotes the redistribution of transferrin receptors to the cell surface. Furthermore, expression of EFA6 induces actin‐based membrane ruffles that are inhibited by co‐expression of dominant‐inhibitory mutant forms of ARF6 or Rac1. Our results demonstrate that by catalyzing nucleotide exchange on ARF6 at the plasma membrane and by regulating Rac1 activation, EFA6 coordinates endocytosis with cytoskeletal rearrangements.