CED-10-WASP-Arp2/3 signaling axis regulates apoptotic cell corpse engulfment in C. elegans

Dev Biol. 2017 Aug 1;428(1):215-223. doi: 10.1016/j.ydbio.2017.06.005. Epub 2017 Jun 9.

Abstract

Efficient clearance of apoptotic cells is essential for tissue homeostasis in metazoans. Genetic studies in Caenorhabditis elegans have identified signaling cascades that activate CED-10/Rac1 GTPase and promote actin cytoskeletal rearrangement during apoptotic cell engulfment. However, the molecular connection between CED-10 activation and actin reorganization remains elusive. Here, we provide evidence that CED-10 binds to the Arp2/3 nucleation promoting factor WASP; CED-10 recruits WASP and Arp2/3 to apoptotic cell corpses in the phagocytes. The loss of WASP and Arp2/3 impaired cell corpse engulfment. Furthermore, we uncover that a WASP-activating factor SEM-5/GRB2 functions in the phagocytes to promote cell corpse clearance. Together, our results suggest CED-10 reorganizes the actin cytoskeleton by recruiting the WASP-Arp2/3 actin nucleation factors during apoptotic cell engulfment.

Keywords: Actin reorganization; C. elegans; Clearance of apoptotic cells.

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin-Related Protein 2 / genetics*
  • Actin-Related Protein 3 / genetics*
  • Animals
  • Apoptosis / physiology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Enzyme Activation / genetics
  • GRB2 Adaptor Protein / metabolism
  • Phagocytosis / genetics*
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Signal Transduction / genetics
  • rac GTP-Binding Proteins / genetics*

Substances

  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • CED-10 protein, C elegans
  • Caenorhabditis elegans Proteins
  • GRB2 Adaptor Protein
  • RNA, Small Interfering
  • Sem-5 protein, C elegans
  • arx-1 protein, C elegans
  • arx-2 protein, C elegans
  • wsp-1 protein, C elegans
  • rac GTP-Binding Proteins