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Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering

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机构: [1]National Clinical Research Center for Geriatrics, West China Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, Sichuan 610065, China [2]Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94305 [3]Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China [4]Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267 [5]State Key Laboratory of Biotherapy, West China Cryo-electron Microscopy Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610065, China [6]Brain and Mind Research Institute and Appel Institute for Alzheimer’s Disease Research, Weill Cornell Medicine, New York, NY 10021 [7]Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200230, China [8]HHMI, Stanford University, Palo Alto, CA 94305 [9]State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
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α-synuclein (α-Syn) is a presynaptic protein that is involved in Parkinson’s and other neurodegenerative diseases and binds to negatively charged phospholipids. Previously, we reported that α-Syn clusters synthetic proteoliposomes that mimic synaptic vesicles. This vesicle-clustering activity depends on a specific interaction of α-Syn with anionic phospholipids. Here, we report that α-Syn surprisingly also interacts with the neutral phospholipid lysophosphatidylcholine (lysoPC). Even in the absence of anionic lipids, lysoPC facilitates α-Syn-induced vesicle clustering but has no effect on Ca2+-triggered fusion in a single vesicle–vesicle fusion assay. The A30P mutant of α-Syn that causes familial Parkinson disease has a reduced affinity to lysoPC and does not induce vesicle clustering. Taken together, the α-Syn–lysoPC interaction may play a role in α-Syn function.

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出版当年[2023]版:
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2023]版:
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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第一作者机构: [1]National Clinical Research Center for Geriatrics, West China Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu, Sichuan 610065, China [2]Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94305
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通讯机构: [2]Department of Molecular and Cellular Physiology, Stanford University, Palo Alto, CA 94305 [3]Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China [8]HHMI, Stanford University, Palo Alto, CA 94305 [9]State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
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