title: Putting a brake on synaptic vesicle endocytosis.
abstract: In chemical synapses, action potentials evoke synaptic vesicle fusion with the presynaptic membrane at the active zone to release neurotransmitter. Synaptic vesicle endocytosis (SVE) then follows exocytosis to recapture vesicle proteins and lipid components for recycling and the maintenance of membrane homeostasis. Therefore, SVE plays an essential role during neurotransmission and is one of the most precisely regulated biological processes. Four modes of SVE have been characterized and both positive and negative regulators have been identified. However, our understanding of SVE regulation remains unclear, especially the identity of negative regulators and their mechanisms of action. Here, we review the current knowledge of proteins that function as inhibitors of SVE and their modes of action in different forms of endocytosis. We also propose possible physiological roles of such negative regulation. We believe that a better understanding of SVE regulation, especially the inhibitory mechanisms, will shed light on neurotransmission in health and disease.
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Capital Medical University, Key Laboratory for the Neurodegenerative Disorders of the Chinese Ministry of Education, Beijing, China.
authors.forename: Ya-Long
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Capital Medical University, Key Laboratory for the Neurodegenerative Disorders of the Chinese Ministry of Education, Beijing, China. clairexizhang@ccmu.edu.cn.
authors.forename: Claire Xi
authors.identifier: 0000-0002-4687-039X
authors.initials: CX
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D060066:Protein Interaction Maps; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism*; D050857:Synaptotagmins / Q000378:metabolism; D013696:Temperature
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; C491861:CABIN1 protein, human; D050857:Synaptotagmins; D051360:Cyclin-Dependent Kinase 5; D019703:Calcineurin; D002154:Calpain
keywords: BDNF; Cain; Calpain; Cdk5; Cl−; Endocytosis inhibitor; Osmotic pressure; Physiological temperature; Synaptotagmin