title: Synaptotagmin modulation of fusion pore kinetics in regulated exocytosis of dense-core vesicles.
abstract: In the exocytosis of neurotransmitter, fusion pore opening represents the first instant of fluid contact between the vesicle lumen and extracellular space. The existence of the fusion pore has been established by electrical measurements, but its molecular composition is unknown. The possibility that synaptotagmin regulates fusion pores was investigated with amperometry to monitor exocytosis of single dense-core vesicles. Overexpression of synaptotagmin I prolonged the time from fusion pore opening to dilation, whereas synaptotagmin IV shortened this time. Both synaptotagmin isoforms reduced norepinephrine flux through open fusion pores. Thus, synaptotagmin interacts with fusion pores, possibly by associating with a core complex of membrane proteins and/or lipid.
authors.affiliation: Department of Physiology, University of Wisconsin Medical School, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: C T
authors.initials: CT
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Grishanin
authors.forename: C A
authors.initials: CA
authors.lastname: Earles
authors.forename: P Y
authors.initials: PY
authors.lastname: Chang
authors.forename: T F
authors.initials: TF
authors.lastname: Martin
authors.forename: E R
authors.initials: ER
authors.lastname: Chapman
authors.forename: M B
authors.initials: MB
authors.lastname: Jackson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020865:Calcium Channels, P-Type / Q000378:metabolism; D020907:Calcium Channels, Q-Type / Q000378:metabolism; D002135:Calcium-Binding Proteins; D021961:Cell Membrane Structures / Q000378:metabolism*; D002864:Chromogranins / Q000378:metabolism; D004594:Electrophysiology; D005089:Exocytosis; D007700:Kinetics; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D016716:PC12 Cells; D020033:Protein Isoforms; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism; D050863:Synaptotagmin I; D050857:Synaptotagmins
chemical_list: D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D002135:Calcium-Binding Proteins; D002864:Chromogranins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; C494294:Syt4 protein, rat; D050857:Synaptotagmins; D002118:Calcium; D009638:Norepinephrine