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An Elmo‐like protein that negatively regulates F‐actin dynamics
Author(s) -
Isik Nilgun,
Brzostowski Joseph,
Jin Tian
Publication year - 2008
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.22.2_supplement.292
Subject(s) - pseudopodia , microbiology and biotechnology , actin , actin cytoskeleton , lamellipodium , biology , cytoskeleton , mdia1 , chemistry , cell , biochemistry
ELMO is a conserved family of proteins that, in complex with DOCK180, function as a GEF to regulate the small GTPase Rac, leading to actin polymerization during cell migration and phagocytosis. We have identified a unique elmo‐like gene, elmo A, in the soil amoeba D. discoideum that appears to function as a negative regulator of Rac activity and actin polymerization. In the absence of ELMO A, cells display an increased rate of phagocytosis and show increased pseudopod formation and excessive F‐actin localization within pseudopods. In response to chemoattractant stimulation, null cells show increased F‐actin levels and a correlative increase in Rac activity, opposite to the GEF activity described for metazoan ELMO/DOCK180; these phenotypes are rescued with the over‐expression of ELMO‐A. TIRF microscopy reveals that a fraction of ELMO‐A localizes near the presumptive actin cortex and is displaced during actin polymerization events, consistent with a negative regulatory role. Pull‐down experiments show that ELMO‐A associates with actin and the myosin II heavy chain. Taken together, our data suggest a novel link from G‐protein coupled receptor to the actin cytoskeleton via ELMO‐A. This research was supported by the Intramural Research Program of NIH, NIAID.