title: Small GTPase CDC-42 promotes apoptotic cell corpse clearance in response to PAT-2 and CED-1 in C. elegans.
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.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: L J
authors.initials: LJ
authors.lastname: Neukomm
authors.affiliation: 1] Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland [2] PhD Program in Molecular Life Sciences (MLS), University of Zurich/ETH Zurich, Zurich, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: A P
authors.initials: AP
authors.lastname: Frei
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: P A
authors.initials: PA
authors.lastname: Huegli
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
authors.forename: M O
authors.initials: MO
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D039641:Integrin beta Chains / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: C407268:CED-10 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D039641:Integrin beta Chains; D008565:Membrane Proteins; C504362:UIG-1 protein, C elegans; C411729:UNC-112 protein, C elegans; C081779:cdc-42 protein, C elegans; C422043:ced-1 protein, C elegans; C093515:pat-3 protein, C elegans; D019204:GTP-Binding Proteins; D020559:Monomeric GTP-Binding Proteins; D020744:rac GTP-Binding Proteins