CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration

Tina L. Gumienny, Enrico Brugnera, Annie Carole Tosello-Trampont, Jason M. Kinchen, Lisa B. Haney, Kiyoji Nishiwaki, Scott F. Walk, Michael E. Nemergut, Ian G. Macara, Ross Francis, Tim Schedl, Yi Qin, Linda Van Aelst, Michael O. Hengartner, Kodimangalam S. Ravichandran

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408 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)27-41
Number of pages15
JournalCell
Volume107
Issue number1
DOIs
StatePublished - Oct 5 2001

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    Gumienny, T. L., Brugnera, E., Tosello-Trampont, A. C., Kinchen, J. M., Haney, L. B., Nishiwaki, K., Walk, S. F., Nemergut, M. E., Macara, I. G., Francis, R., Schedl, T., Qin, Y., Van Aelst, L., Hengartner, M. O., & Ravichandran, K. S. (2001). CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell, 107(1), 27-41. https://doi.org/10.1016/S0092-8674(01)00520-7