TY - JOUR
T1 - CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration
AU - Gumienny, Tina L.
AU - Brugnera, Enrico
AU - Tosello-Trampont, Annie Carole
AU - Kinchen, Jason M.
AU - Haney, Lisa B.
AU - Nishiwaki, Kiyoji
AU - Walk, Scott F.
AU - Nemergut, Michael E.
AU - Macara, Ian G.
AU - Francis, Ross
AU - Schedl, Tim
AU - Qin, Yi
AU - Van Aelst, Linda
AU - Hengartner, Michael O.
AU - Ravichandran, Kodimangalam S.
N1 - Funding Information:
We are indebted to Mona Spector and members of the Hengartner and Ravichandran labs for advice and reagents. We are grateful to Michelle Cilia, Heather Cosel-Pieper, Sambath Chung, Monica Driscoll, Asako Sugimoto, Muneyoshi Otori, Stephen Wick, Ronald Plasterk, Yuji Kohara, Min Han, Peter Reddien, Bob Nakamoto, and Michiyuki Matsuda for invaluable assistance at various stages of this work. We thank Michael Weber, David Brautigan, Amy Bouton, Ulrike Lorenz, and Jim Casanova for comments on the manuscript. This work was supported in part by grant NIH-GM52540 and a research grant from Devgen NV (Belgium) (M.O.H), grant NIH-GM63310 (T.S.), and by grants from the National Institutes of Health and American Cancer Society (K.S.R.).
PY - 2001/10/5
Y1 - 2001/10/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=17944376439&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(01)00520-7
DO - 10.1016/S0092-8674(01)00520-7
M3 - Article
C2 - 11595183
AN - SCOPUS:17944376439
SN - 0092-8674
VL - 107
SP - 27
EP - 41
JO - Cell
JF - Cell
IS - 1
ER -