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四川大学华西医院[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四川大学华西医院[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
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.
基金:
National Key R&D
Program of China (2019YFE0120600) and the CAS Project for Young Scientists
in Basic Research (YSBR-095); Y.L. thanks the support from the National Natural
Science Foundation of China (31900688 and 32170686). This research was supported by the NIH (R01NS121077 to J.D. and J.B., R01NS102181, R01NS113960,
1RF1NS126342, and R21NS127939 to J.B., P50NS094733 and R01NS077906
to T.C.S., and R01MH063105 to A.T.B.).
语种:
外文
PubmedID:
中科院(CAS)分区:
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
第一作者:
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
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Lai Ying,Zhao Chunyu,Tian Zhiqi,et al.Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering[J].Proceedings of the National Academy of Sciences of the United States of America.2023,120(44):e2310174120.doi:10.1073/pnas.2310174120.
APA:
Lai Ying,Zhao Chunyu,Tian Zhiqi,Wang Chuchu,Fan Jiaqi...&Diao Jiajie.(2023).Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering.Proceedings of the National Academy of Sciences of the United States of America,120,(44)
MLA:
Lai Ying,et al."Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering".Proceedings of the National Academy of Sciences of the United States of America 120..44(2023):e2310174120