title: Clathrin and AP2 are required for phagocytic receptor-mediated apoptotic cell clearance in Caenorhabditis elegans.
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.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Didi
authors.initials: D
authors.lastname: Chen
authors.forename: Youli
authors.initials: Y
authors.lastname: Jian
authors.forename: Xuezhao
authors.initials: X
authors.lastname: Liu
authors.forename: Yuanya
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liang
authors.forename: Xiaying
authors.initials: X
authors.lastname: Qi
authors.forename: Hongwei
authors.initials: H
authors.lastname: Du
authors.forename: Wei
authors.initials: W
authors.lastname: Zou
authors.forename: Lianwan
authors.initials: L
authors.lastname: Chen
authors.forename: Yongping
authors.initials: Y
authors.lastname: Chai
authors.forename: Guangshuo
authors.initials: G
authors.lastname: Ou
authors.forename: Long
authors.initials: L
authors.lastname: Miao
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Chonglin
authors.initials: C
authors.lastname: Yang
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D033922:Clathrin Heavy Chains / Q000378:metabolism; D004705:Endocytosis; D005854:Germ Cells / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics* / Q000502:physiology; D010588:Phagosomes / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D033962:Adaptor Protein Complex 2; D051017:Apoptosis Regulatory Proteins; C112888:CED-6 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002966:Clathrin; D008565:Membrane Proteins; D010750:Phosphoproteins; C422043:ced-1 protein, C elegans; C535031:chc-1 protein, C elegans; D033922:Clathrin Heavy Chains