SLI-1 Cbl inhibits the engulfment of apoptotic cells in C. elegans through a ligase-independent function.

SLI-1 Cbl inhibits the engulfment of apoptotic cells in C. elegans through a ligase-independent function.

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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 wilds of eldraine prerelease guide 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 anodized pearl price xbox 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.