Focal adhesion components are essential for mammalian cell cytokinesis.
The final stages in mammalian cytokinesis are poorly understood. Previously, we reported that the ADP-ribosyltransferase activity of Pseudomonas aeruginosa type III secreted toxin ExoT inhibits late stages of cytokinesis. Given that Crk adaptor proteins are the major substrates of ExoT ADP-ribosyltransferase activity, we tested the involvement of Crk in cytokinesis. We report that the focal adhesion-associated proteins, Crk and paxillin are essential for completion of cytokinesis. When their function is absent, the cytoplasmic bridge fails to resolve and the daughter cells fuse to form a binucleated cell. During cytokinesis, Crk is required for syntaxin-2 recruitment to the midbody, while paxillin is required for both Crk and syntaxin-2 localization to this compartment. Our data demonstrate that the subcellular localization and the activity of RhoA and citron K, which are essential for early stages of cytokinesis, are not dependent on paxillin, Crk or syntaxin-2. These studies reveal a novel role for Crk and paxillin in cytokinesis and suggest that focal adhesion complex, as a unit, may partake in this fundamental cellular process.
Shafikhani
Sasha H
SH
Department of Medicine, University of California, San Francisco, California, USA.
Mostov
Keith
K
Engel
Joanne
J
D000818:Animals; D002461:Cell Line, Transformed; D048749:Cytokinesis; D022001:Focal Adhesions / Q000201:enzymology / Q000378:metabolism*; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D050737:Proto-Oncogene Proteins c-crk / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D050827:Syntaxin 1 / Q000378:metabolism
C485285:CRK protein, human; D051419:Paxillin; D020033:Protein Isoforms; D050737:Proto-Oncogene Proteins c-crk; D050827:Syntaxin 1; D016392:Proto-Oncogene Proteins pp60(c-src)
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