Synaptotagmin-1 is a bidirectional Ca2+ sensor for neuronal endocytosis

被引：20

作者：

Chen, Yang ^{[1
,2
]}

Hu, Shaoqin ^{[1
]}

Wu, Xuanang ^{[1
]}

Xie, Zhenli ^{[1
,3
,4
,5
]}

Wang, Yuan ^{[4
,5
]}

Wang, Bianbian ^{[1
,6
]}

Li, Xiaopeng ^{[1
,6
]}

Pei, Yingmei ^{[1
]}

Gu, Yuhao ^{[1
]}

Huang, Kai ^{[1
,7
]}

Huo, Jingxiao ^{[1
]}

Wei, Anqi ^{[1
]}

Bi, Cheng ^{[1
]}

Lu, Zhe ^{[1
]}

Song, Qian ^{[1
]}

Xu, Huadong ^{[8
]}

Kang, Xinjiang ^{[6
,8
]}

Shao, Shuli ^{[9
]}

Long, Jiangang ^{[1
]}

Liu, Jiankang ^{[1
]}

Zhou, Zhuan ^{[4
,5
]}

Huang, Rong ^{[4
,5
]}

Chai, Zuying ^{[4
,5
]}

Wang, Changhe ^{[1
,2
,3
,8
]}

机构：

[1] Xi An Jiao Tong Univ, Key Lab Biomed Informat Engn, Inst Mitochondrial Biol & Med, Sch Life Sci & Technol,Neurosci Res Ctr,Minist Ed, Xian 710049, Shaanxi, Peoples R China

[2] Xi An Jiao Tong Univ, Dept Neurol, Affiliated Hosp 1, Xian 710061, Peoples R China

[3] Xi An Jiao Tong Univ, Core Facil Sharing Platform, Xian 710049, Peoples R China

[4] Peking Univ, Inst Mol Med, State Key Lab Membrane Biol, Beijing 100871, Peoples R China

[5] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[6] Liaocheng Univ, Coll Life Sci, Liaocheng 252059, Shandong, Peoples R China

[7] Qingdao Agr Univ, Haidu Coll, Qingdao 265200, Peoples R China

[8] Southwest Med Univ, Inst Cardiovasc Res, Key Lab Med Electrophysiol, Minist Educ China, Luzhou 646000, Peoples R China

[9] Qiqihar Univ, Coll Life Sci Forestry & Agr, Qiqihar 161004, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2022年 / 119卷 / 20期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

synaptotagmin; clathrin-mediated endocytosis; bulk endocytosis; Ca2+; membrane tubulation; SYNAPTIC VESICLE ENDOCYTOSIS; CALCIUM; FUSION; EXOCYTOSIS; DEPENDENCE; SECRETION; MEMBRANE; KINETICS; TRIGGERS; BINDING;

D O I：

10.1073/pnas.2111051119

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Exocytosis and endocytosis are tightly coupled. In addition to initiating exocytosis, Ca2+ plays critical roles in exocytosis-endocytosis coupling in neurons and nonneuronal cells. Both positive and negative roles of Ca2+ in endocytosis have been reported; however, Ca2+ inhibition in endocytosis remains debatable with unknown mechanisms. Here, we show that synaptotagmin-1 (Syt1), the primary Ca2+ sensor initiating exocytosis, plays bidirectional and opposite roles in exocytosis-endocytosis coupling by promoting slow, small-sized clathrin-mediated endocytosis but inhibiting fast, large-sized bulk endocytosis. Ca2+-binding ability is required for Syt1 to regulate both types of endocytic pathways, the disruption of which leads to inefficient vesicle recycling under mild stimulation and excessive membrane retrieval following intense stimulation. Ca2+-dependent membrane tubulation may explain the opposite endocytic roles of Syt1 and provides a general membrane-remodeling working model for endocytosis determination. Thus, Syt1 is a primary bidirectional Ca2+ sensor facilitating clathrin-mediated endocytosis but clamping bulk endocytosis, probably by manipulating membrane curvature to ensure both efficient and precise coupling of endocytosis to exocytosis.

引用

页数：12

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[1] Synaptotagmin-1 and-7 Are Redundantly Essential for Maintaining the Capacity of the Readily-Releasable Pool of Synaptic Vesicles [J].