title: Exocytosis and endocytosis: modes, functions, and coupling mechanisms.
abstract: Vesicle exocytosis releases content to mediate many biological events, including synaptic transmission essential for brain functions. Following exocytosis, endocytosis is initiated to retrieve exocytosed vesicles within seconds to minutes. Decades of studies in secretory cells reveal three exocytosis modes coupled to three endocytosis modes: (a) full-collapse fusion, in which vesicles collapse into the plasma membrane, followed by classical endocytosis involving membrane invagination and vesicle reformation; (b) kiss-and-run, in which the fusion pore opens and closes; and (c) compound exocytosis, which involves exocytosis of giant vesicles formed via vesicle-vesicle fusion, followed by bulk endocytosis that retrieves giant vesicles. Here we review these exo- and endocytosis modes and their roles in regulating quantal size and synaptic strength, generating synaptic plasticity, maintaining exocytosis, and clearing release sites for vesicle replenishment. Furthermore, we highlight recent progress in understanding how vesicle endocytosis is initiated and is thus coupled to exocytosis. The emerging model is that calcium influx via voltage-dependent calcium channels at the calcium microdomain triggers endocytosis and controls endocytosis rate; calmodulin and synaptotagmin are the calcium sensors; and the exocytosis machinery, including SNARE proteins (synaptobrevin, SNAP25, and syntaxin), is needed to coinitiate endocytosis, likely to control the amount of endocytosis.
authors.affiliation: National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892; email: wul@ninds.nih.gov , edaeni.hamid@nih.gov.
authors.forename: Ling-Gang
authors.initials: LG
authors.lastname: Wu
authors.forename: Edaeni
authors.initials: E
authors.lastname: Hamid
authors.forename: Wonchul
authors.initials: W
authors.lastname: Shin
authors.forename: Hsueh-Cheng
authors.initials: HC
authors.lastname: Chiang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology; D013572:Synaptic Vesicles / Q000502:physiology / Q000648:ultrastructure; D050857:Synaptotagmins / Q000502:physiology
chemical_list: D015220:Calcium Channels; D002147:Calmodulin; D050857:Synaptotagmins; D002118:Calcium