RRC ID 46258
Author Anderson C, Zhou S, Sawin E, Horvitz HR, Hurwitz ME.
Title SLI-1 Cbl inhibits the engulfment of apoptotic cells in C. elegans through a ligase-independent function.
Journal PLoS Genet
Abstract The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway, which includes the small GTPase CED-10 Rac and the cytoskeletal regulator ABI-1, acts to rearrange the cytoskeleton of the engulfing cell. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The second pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Cbl, the mammalian homolog of the C. elegans E3 ubiquitin ligase and adaptor protein SLI-1, interacts with Rac and Abi2 and modulates the actin cytoskeleton, suggesting it might act in engulfment. Our genetic studies indicate that SLI-1 inhibits apoptotic cell engulfment and DTC migration independently of the CED-10 Rac and CED-1 pathways. We found that the RING finger domain of SLI-1 is not essential to rescue the effects of SLI-1 deletion on cell migration, suggesting that its role in this process is ubiquitin ligase-independent. We propose that SLI-1 opposes the engulfment of apoptotic cells via a previously unidentified pathway.
Volume 8(12)
Pages e1003115
Published 2012-1-1
DOI 10.1371/journal.pgen.1003115
PII PGENETICS-D-12-01786
PMID 23271977
PMC PMC3521709
MeSH Actin Cytoskeleton / genetics Actin Cytoskeleton / metabolism Animals Apoptosis* Caenorhabditis elegans* / cytology Caenorhabditis elegans* / growth & development Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cell Movement* Cytoskeletal Proteins / genetics Cytoskeletal Proteins / metabolism Gonads / growth & development Membrane Proteins / genetics Membrane Proteins / metabolism Phagocytosis Proto-Oncogene Proteins c-cbl* / genetics Proto-Oncogene Proteins c-cbl* / metabolism Signal Transduction rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism
IF 5.175
Times Cited 21
WOS Category GENETICS & HEREDITY
Resource
C.elegans tm494