CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration.
The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phagocytosis of apoptotic cells and cell motility. Here, we describe an additional member of this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2. In C. elegans, CED-12 is required for engulfment of dying cells and for cell migrations. In mammalian cells, ELMO1 functionally cooperates with CrkII and Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements. These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals.
Gumienny
T L
TL
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11743, USA.
Brugnera
E
E
Tosello-Trampont
A C
AC
Kinchen
J M
JM
Haney
L B
LB
Nishiwaki
K
K
Walk
S F
SF
Nemergut
M E
ME
Macara
I G
IG
Francis
R
R
Schedl
T
T
Qin
Y
Y
Van Aelst
L
L
Hengartner
M O
MO
Ravichandran
K S
KS
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D005434:Flow Cytometry; D017238:Genes, Helminth; D017930:Genes, Reporter; D006066:Gonads / Q000254:growth & development; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010587:Phagocytosis / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; 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; D003598:Cytoskeletal Proteins; C099818:DOCK1 protein, human; C486678:ELMO2 protein, human; C486679:ELMO3 protein, human; C544335:Elmo2 protein, mouse; D015801:Helminth Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins; D011494:Protein Kinases; D020744:rac GTP-Binding Proteins