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Complexity of ARF Function in the Cell Periphery
Author(s) -
Cohen Lee Ann,
Varnai Peter,
Balla Tamas,
Donaldson Julie G
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a617-d
Subject(s) - microbiology and biotechnology , focal adhesion , guanine nucleotide exchange factor , membrane ruffling , cell migration , cytoskeleton , lamellipodium , gtpase , cell , golgi apparatus , rac1 , gene knockdown , cell adhesion , chemistry , biology , signal transduction , biochemistry , gene , endoplasmic reticulum
ARNO/cytohesin family proteins, are BFA insensitive exchange factors (GEFs) for ARF small GTPases that function in the cell periphery where they can promote cell ruffling at the PM, and promote cell migration. We show that ARNO/cytohesin GEFs are recruited by active ARF6 onto the plasma membrane through an interaction between their carboxy terminal PH domains, GTP Arf6 and inositol phospholipids. Once recruited to the plasma membrane ARNO/cytohesin family GEFs can recruit and activate ARF1 at the PM. This led us to examine a role for ARF1 in the organization of cytoskeletal proteins in the cell periphery. siRNA mediated knockdown of ARF1 leaves the Golgi intact, but alters the structure of focal adhesions in HeLa cells. Knockdown of ARF1, but not ARF6, severely retards cell spreading, and inhibits cell migration. These studies support an under appreciated requirement of ARF1 in cytoskeletal and focal adhesion organization in the cell periphery.