RRC ID 45945
Author Chen D, Jian Y, Liu X, Zhang Y, Liang J, Qi X, Du H, Zou W, Chen L, Chai Y, Ou G, Miao L, Wang Y, Yang C.
Title Clathrin and AP2 are required for phagocytic receptor-mediated apoptotic cell clearance in Caenorhabditis elegans.
Journal PLoS Genet
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.
Volume 9(5)
Pages e1003517
Published 2013-5-1
DOI 10.1371/journal.pgen.1003517
PMID 23696751
PMC PMC3656144
MeSH 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
IF 5.175
Times Cited 15
C.elegans tm2423 tm1125