学术报告
题目：Apoptotic cell on road: from the cell membrane to lysosomes
报告人：Chonglin Yang, Ph.D.
Center for Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
时间： Thursday 9:00 a.m., June 7
地点：金光生科大楼 610 会议室
Appropriate clearance of apoptotic cells is critical to tissue remodeling, suppression of inflammation, and control of immune responses. The mechanisms governing apoptotic cell removal is, however, not well understood. To this end, we take advantage of the powerful genetic tools in C. elegans, combined with approaches of cell biology and biochemistry, to identify novel regulators required for cell corpse clearance. Our studies have revealed several protein complexes acting in the phagocytic receptor CED-1-mediated pathway by regulating distinct signaling events. 1) We found that the C. elegans intracellular protein sorting complex, retromer, mediates the recycling of CED-1 from phagosomes to the cell membrane. 2) We identified clathrin and the AP2 complex, the central players of clathrin-mediated endocytosis (CME), as essential players in CED-1-mediated cell corpse clearance by acting downstream of CED-1 and regulating the cytoskeletal rearrangement required for corpse engulfment. They also play a critical role in phagosome maturation necessary for corpse degradation. 3) We found that the HOPS complex, which is required for biogenesis of endocytic organelles, affects apoptotic cell degradation by mediating phagolysosome formation.
As lysosomes are central to the degradation of apoptotic cells, endoctyosed cargoes, as well as autophagic materials, we also focus our research on genetic control of lysosome homeostasis. Using genetic screen and gene cloning we have identified novel genes required for size control of lysosomes and other endocytic organelles. Loss of function of these genes impairs either cell corpse degradation or other cellular processes. In addition, we have applied worms to chemical screen and obtained compounds that specifically interfere with lysosome dynamics. Altogether we hope that our genetic and chemical-genetic studies on lysosomes in C. elegans will contribute in a major way to our understanding of lysosome homeostasis and functions, and lysosome-related human diseases.
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