Clathrin and AP2 Are Required for Phagocytic Receptor-Mediated Apoptotic Cell Clearance in Caenorhabditis Elegans

PLoS Genet. 2013 May;9(5):e1003517. doi: 10.1371/journal.pgen.1003517. Epub 2013 May 16.

Abstract

Clathrin and the multi-subunit adaptor protein complex AP2 are central players in clathrin-mediated endocytosis by which the cell selectively internalizes surface materials. Here, we report the essential role of clathrin and AP2 in phagocytosis of apoptotic cells. In Caenorhabditis elegans, depletion of the clathrin heavy chain CHC-1 and individual components of AP2 led to a significant accumulation of germ cell corpses, which resulted from defects in both cell corpse engulfment and phagosome maturation required for corpse removal. CHC-1 and AP2 components associate with phagosomes in an inter-dependent manner. Importantly, we found that the phagocytic receptor CED-1 interacts with the α subunit of AP2, while the CED-6/Gulp adaptor forms a complex with both CHC-1 and the AP2 complex, which likely mediates the rearrangement of the actin cytoskeleton required for cell corpse engulfment triggered by the CED-1 signaling pathway. In addition, CHC-1 and AP2 promote the phagosomal association of LST-4/Snx9/18/33 and DYN-1/dynamin by forming a complex with them, thereby facilitating the maturation of phagosomes necessary for corpse degradation. These findings reveal a non-classical role of clathrin and AP2 and establish them as indispensable regulators in phagocytic receptor-mediated apoptotic cell clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Protein Complex 2 / genetics
  • Adaptor Protein Complex 2 / metabolism*
  • Animals
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism
  • Clathrin / genetics
  • Clathrin / metabolism*
  • Clathrin Heavy Chains / metabolism
  • Endocytosis
  • Germ Cells / pathology
  • Membrane Proteins / metabolism
  • Phagocytosis / genetics*
  • Phagocytosis / physiology
  • Phagosomes / genetics
  • Phagosomes / metabolism
  • Phosphoproteins / metabolism
  • Signal Transduction

Substances

  • Adaptor Protein Complex 2
  • Apoptosis Regulatory Proteins
  • CED-6 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Clathrin
  • Membrane Proteins
  • Phosphoproteins
  • ced-1 protein, C elegans
  • chc-1 protein, C elegans
  • Clathrin Heavy Chains

Grant support

This research was supported by grants from the National Science Foundation of China (31025015 and 31230043 to CY, and 31071214 to YJ) and the National Basic Research Program of China (2011CB910102 and 2013CB910102). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.