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

Dou Wu1, Yongping Chai1, Zhiwen Zhu1

  • 1Tsinghua-Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing 100084, China.

Developmental Biology
|June 13, 2017
PubMed

Insights

Efficiently clearing apoptotic cells requires CED-10/Rac1 GTPase to recruit WASP and Arp2/3. This mechanism reorganizes the actin cytoskeleton, promoting cell corpse engulfment and tissue homeostasis.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Efficient clearance of apoptotic cells is crucial for maintaining tissue homeostasis in multicellular organisms.
  • Signaling pathways involving CED-10/Rac1 GTPase have been linked to actin cytoskeletal rearrangement during the engulfment of apoptotic cells.

Purpose of the Study:

  • To elucidate the molecular link between CED-10 activation and actin reorganization during apoptotic cell engulfment.
  • To identify the specific factors involved in CED-10-mediated actin remodeling in phagocytes.

Main Methods:

  • Genetic studies in Caenorhabditis elegans.
  • Analysis of protein-protein interactions between CED-10, WASP, and Arp2/3.
  • Investigating the role of SEM-5/GRB2 in phagocyte function.

Main Results:

  • CED-10 directly binds to the Arp2/3 nucleation-promoting factor WASP.
  • CED-10 recruits WASP and Arp2/3 complex to apoptotic cell corpses within phagocytes.
  • Loss of WASP or Arp2/3 function significantly impairs apoptotic cell corpse engulfment.
  • The WASP-activating factor SEM-5/GRB2 plays a role in promoting cell corpse clearance within phagocytes.

Conclusions:

  • CED-10 orchestrates actin cytoskeleton reorganization during apoptotic cell engulfment by recruiting the WASP-Arp2/3 complex.
  • The SEM-5/GRB2 pathway is essential for activating WASP and facilitating efficient phagocytosis of apoptotic cells.
  • This study reveals a key molecular mechanism underlying efferocytosis and tissue homeostasis.
Keywords:
Actin reorganizationC. elegansClearance of apoptotic cells

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