C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment.
We have identified and characterized a novel C. elegans gene, ced-12, that functions in the conserved GTPase signaling pathway mediated by CED-2/Crkll, CED-5/DOCK180, and CED-10/Rac to control cell migration and phagocytosis of apoptotic cells. We provide evidence that ced-12 likely acts upstream of ced-10 during cell migration and phagocytosis and that CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro. We propose that the formation and localization of a CED-2-CED-5-CED-12 ternary complex to the plasma membrane activates CED-10, leading to the cytoskeletal reorganization that occurs in the polarized extension of cell surfaces in engulfing cells and migrating cells. We suggest that CED-12 counterparts in higher organisms regulate cytoskeleton dynamics, as CED-12 does in C. elegans.
Wu
Y C
YC
Department of Zoology, National Taiwan University, Taipei. yichun@ccms.ntu.edu.tw
Tsai
M C
MC
Cheng
L C
LC
Chou
C J
CJ
Weng
N Y
NY
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D015801:Helminth Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C407268:CED-10 protein, C elegans; C438369:CED-12 protein, C elegans; C111579:CED-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C099818:DOCK1 protein, human; D015801:Helminth Proteins; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D011494:Protein Kinases; D020744:rac GTP-Binding Proteins