title: Synaptotagmin-11 inhibits clathrin-mediated and bulk endocytosis.
abstract: Precise and efficient endocytosis is essential for vesicle recycling during a sustained neurotransmission. The regulation of endocytosis has been extensively studied, but inhibitors have rarely been found. Here, we show that synaptotagmin-11 (Syt11), a non-Ca(2+)-binding Syt implicated in schizophrenia and Parkinson's disease, inhibits clathrin-mediated endocytosis (CME) and bulk endocytosis in dorsal root ganglion neurons. The frequency of both types of endocytic event increases in Syt11 knockdown neurons, while the sizes of endocytosed vesicles and the kinetics of individual bulk endocytotic events remain unaffected. Specifically, clathrin-coated pits and bulk endocytosis-like structures increase on the plasma membrane in Syt11-knockdown neurons. Structural-functional analysis reveals distinct domain requirements for Syt11 function in CME and bulk endocytosis. Importantly, Syt11 also inhibits endocytosis in hippocampal neurons, implying a general role of Syt11 in neurons. Taken together, we propose that Syt11 functions to ensure precision in vesicle retrieval, mainly by limiting the sites of membrane invagination at the early stage of endocytosis.
authors.affiliation: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and PKU-IDG/McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China College of Life Sciences, Forestry and Agriculture, Qiqihar University, Qiqihar, China.
authors.forename: Changhe
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and PKU-IDG/McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Yeshi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and PKU-IDG/McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Meiqin
authors.initials: M
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and PKU-IDG/McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Zuying
authors.initials: Z
authors.lastname: Chai
authors.affiliation: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and PKU-IDG/McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Qihui
authors.initials: Q
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and PKU-IDG/McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, Agency for Science, Technology, and Research, Singapore City, Singapore Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore.
authors.forename: Weiping
authors.initials: W
authors.lastname: Han
authors.affiliation: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and PKU-IDG/McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China clairexizhang@ccmu.edu.cn.
authors.forename: Claire Xi
authors.initials: CX
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and PKU-IDG/McGovern Institute for Brain Research and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002966:Clathrin / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000502:physiology*; D004705:Endocytosis; D005089:Exocytosis; D005727:Ganglia, Spinal / Q000166:cytology; D055785:Gene Knockdown Techniques; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D050857:Synaptotagmins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002966:Clathrin; D050857:Synaptotagmins
keywords: bulk endocytosis; clathrin‐mediated endocytosis; exocytosis; synaptotagmin‐11; vesicle recycling