Nuclear localization of the DOCK180/ELMO complex.
DOCK180 protein plays a key role during development, cell motility, and phagocytosis. It forms a complex with another protein ELMO, and this complex acts as a guanine nucleotide exchange factor (GEF) for Rac. However, DOCK180-containing complexes have not been purified by unbiased biochemical approaches, and the nature and subcellular localization of these complexes remain unclear. Here, we show that a large fraction of endogenous DOCK180 is present as a 700kDa nuclear complex with ELMO proteins. In addition, this nuclear DOCK180/ELMO complex has functional Rac-GEF activity. Furthermore, endogenous DOCK180 could be found in complexes with different ELMO isoforms (ELMO1, 2 or 3) in different cell lines, depending on the ELMO isoforms expressed. These studies suggest that DOCK180 may associate with different ELMO proteins to form cell-type specific complexes and may have functions in both the nucleus and the cytoplasm.
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MA 21224, USA.
Jinhu
J
Yin
Lisa
L
Haney
Scott
S
Walk
Sharleen
S
Zhou
Kodi S
KS
Ravichandran
Weidong
W
Wang
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D016466:CHO Cells; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002457:Cell Extracts / Q000032:analysis; D002467:Cell Nucleus / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D014018:Tissue Distribution; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C438369:CED-12 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002457:Cell Extracts; D003598:Cytoskeletal Proteins; C099818:DOCK1 protein, human; C465214:ELMO1 protein, human; D020033:Protein Isoforms; D020744:rac GTP-Binding Proteins