RRC ID 45814
Author Neukomm LJ, Zeng S, Frei AP, Huegli PA, Hengartner MO.
Title Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans.
Journal Cell Death Differ
Abstract The rapid clearance of dying cells is important for the well-being of multicellular organisms. In C. elegans, cell corpse removal is mainly mediated by three parallel engulfment signaling cascades. These pathways include two small GTPases, MIG-2/RhoG and CED-10/Rac1. Here we present the identification and characterization of CDC-42 as a third GTPase involved in the regulation of cell corpse clearance. Genetic analyses performed by both loss of cdc-42 function and cdc-42 overexpression place cdc-42 in parallel to the ced-2/5/12 signaling module, in parallel to or upstream of the ced-10 module, and downstream of the ced-1/6/7 module. CDC-42 accumulates in engulfing cells at membranes surrounding apoptotic corpses. The formation of such halos depends on the integrins PAT-2/PAT-3, UNC-112 and the GEF protein UIG-1, but not on the canonical ced-1/6/7 or ced-2/5/12 signaling modules. Together, our results suggest that the small GTPase CDC-42 regulates apoptotic cell engulfment possibly upstream of the canonical Rac GTPase CED-10, by polarizing the engulfing cell toward the apoptotic corpse in response to integrin signaling and ced-1/6/7 signaling in C. elegans.
Volume 21(6)
Pages 845-53
Published 2014-6-1
DOI 10.1038/cdd.2014.23
PII cdd201423
PMID 24632947
PMC PMC4013519
MeSH Animals Apoptosis / genetics* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Cell Adhesion Molecules / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* GTP-Binding Proteins / genetics GTP-Binding Proteins / metabolism* Gene Expression Regulation, Developmental Guanine Nucleotide Exchange Factors / metabolism Integrin beta Chains / genetics Membrane Proteins / genetics* Membrane Proteins / metabolism Monomeric GTP-Binding Proteins / genetics Monomeric GTP-Binding Proteins / metabolism Signal Transduction / genetics rac GTP-Binding Proteins / metabolism
IF 10.717
Times Cited 19
C.elegans tm1949 tm1556 tm1826