CED-12/ELMO, a Novel Member of the CrkII/Dock180/Rac Pathway, Is Required for Phagocytosis and Cell Migration

• Published in: Cell Vol. 107; no. 1; pp. 27 - 41
• Main Authors: Gumienny, Tina L., Brugnera, Enrico, Tosello-Trampont, Annie-Carole, Kinchen, Jason M., Haney, Lisa B., Nishiwaki, Kiyoji, Walk, Scott F., Nemergut, Michael E., Macara, Ian G., Francis, Ross, Schedl, Tim, Qin, Yi, Van Aelst, Linda, Hengartner, Michael O., Ravichandran, Kodimangalam S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.10.2001
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans - cytology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; ced-10 gene; CED-12 protein; ced-2 gene; ced-5 gene; Cell Line; Cell Movement - physiology; Cell Surface Extensions - metabolism; crkII gene; Cytoskeletal Proteins; Cytoskeleton - metabolism; dock180 gene; ELMO protein; elmo1 gene; elmo2 gene; Flow Cytometry; Genes, Helminth; Genes, Reporter; Gonads - growth & development; Helminth Proteins - genetics; Helminth Proteins - metabolism; Humans; Male; Mice; Microscopy, Fluorescence; Molecular Sequence Data; Phagocytosis - physiology; Protein Kinases - metabolism; Proteins - metabolism; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-crk; rac GTP-Binding Proteins - metabolism; rac1 gene; Rac1 protein; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Sequence Alignment; Signal Transduction - physiology; Tissue Distribution
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(01)00520-7

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.