Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering-Reference-Cited by-同舟云学术

Neutral lysophosphatidylcholine mediates α-synuclein-induced synaptic vesicle clustering

Published:2023-10-26 Issue:44 Volume:120 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Lai Ying¹²^ORCID,Zhao Chunyu³,Tian Zhiqi⁴^ORCID,Wang Chuchu²³^ORCID,Fan Jiaqi¹,Hu Xiao⁴,Tu Jia³,Li Tihui⁵,Leitz Jeremy²,Pfuetzner Richard A.²,Liu Zhengtao³,Zhang Shengnan³,Su Zhaoming⁵^ORCID,Burré Jacqueline⁶^ORCID,Li Dan⁷^ORCID,Südhof Thomas C.²⁸,Zhu Zheng-Jiang³^ORCID,Liu Cong³⁹^ORCID,Brunger Axel T.²⁸^ORCID,Diao Jiajie⁴^ORCID

Affiliation:

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

Abstract

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 Ca 2+ -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.

Funder

HHS | NIH | National Institute of Neurological Disorders and Stroke

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2310174120

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