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

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...

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Bibliographic Details
Published in:Developmental biology 2017-08, Vol.428 (1), p.215-223
Main Authors: Wu, Dou, Chai, Yongping, Zhu, Zhiwen, Li, Wenjing, Ou, Guangshuo, Li, Wei
Format: Article
Language:English
Subjects:
Actin Cytoskeleton - metabolism
Actin reorganization
Actin-Related Protein 2 - genetics
Actin-Related Protein 3 - genetics
Animals
Apoptosis - physiology
C. elegans
Caenorhabditis elegans - genetics
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - genetics
Caenorhabditis elegans Proteins - metabolism
Clearance of apoptotic cells
Enzyme Activation - genetics
GRB2 Adaptor Protein - metabolism
Phagocytosis - genetics
Protein Binding
rac GTP-Binding Proteins - genetics
RNA Interference
RNA, Small Interfering - genetics
Signal Transduction - genetics
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Summary: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. •CED-10 recruits WASP-Arp2/3 actin nucleation factors to apoptotic cell corpses.•WASP and the Arp2/3 complex are required for efficient clearance of apoptotic cells.•WASP-activating factor SEM-5/GRB2 functions in the phagocyte to promote the apoptotic cell removal.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2017.06.005