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    Synaptotagmin modulation of fusion pore kinetics in regulated exocytosis of dense-core vesicles (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-11-03
    Description: 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, C T -- Grishanin, R -- Earles, C A -- Chang, P Y -- Martin, T F -- Chapman, E R -- Jackson, M B -- New York, N.Y. -- Science. 2001 Nov 2;294(5544):1111-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Wisconsin Medical School, University of Wisconsin, Madison, WI 53706, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11691996" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/metabolism ; Calcium Channels, P-Type/metabolism ; Calcium Channels, Q-Type/metabolism ; *Calcium-Binding Proteins ; Cell Membrane Structures/*metabolism ; Chromogranins/metabolism ; Electrophysiology ; *Exocytosis ; Kinetics ; *Membrane Fusion ; Membrane Glycoproteins/*metabolism ; Membrane Potentials ; Nerve Tissue Proteins/*metabolism ; Neurotransmitter Agents/*metabolism ; Norepinephrine/metabolism ; PC12 Cells ; Protein Isoforms ; Rats ; Recombinant Fusion Proteins/metabolism ; Secretory Vesicles/*metabolism ; Synaptic Transmission ; Synaptic Vesicles/metabolism ; Synaptotagmin I ; Synaptotagmins
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    G protein betagamma subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca2+ entry (2001)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2001-04-17
    Description: The nervous system can modulate neurotransmitter release by neurotransmitter activation of heterotrimeric GTP-binding protein (G protein)-coupled receptors. We found that microinjection of G protein betagamma subunits (Gbetagamma) mimics serotonin's inhibitory effect on neurotransmission. Release of free Gbetagamma was critical for this effect because a Gbetagamma scavenger blocked serotonin's effect. Gbetagamma had no effect on fast, action potential-evoked intracellular Ca2+ release that triggered neurotransmission. Inhibition of neurotransmitter release by serotonin was still seen after blockade of all classical Gbetagamma effector pathways. Thus, Gbetagamma blocked neurotransmitter release downstream of Ca2+ entry and may directly target the exocytotic fusion machinery at the presynaptic terminal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blackmer, T -- Larsen, E C -- Takahashi, M -- Martin, T F -- Alford, S -- Hamm, H E -- New York, N.Y. -- Science. 2001 Apr 13;292(5515):293-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Pharmacology and Biological Chemistry, Department of Physiology, Northwestern University Institute for Neuroscience, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11303105" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Antigens, Surface/metabolism ; Axons/drug effects/*physiology ; Calcium/metabolism ; Calcium Channels/metabolism ; Cyclic AMP-Dependent Protein Kinases/pharmacology ; Excitatory Postsynaptic Potentials/drug effects ; *Exocytosis ; *GTP-Binding Protein beta Subunits ; *GTP-Binding Protein gamma Subunits ; Heterotrimeric GTP-Binding Proteins/*pharmacology ; Ion Channel Gating ; Lampreys ; Membrane Proteins/metabolism ; Microinjections ; Nerve Tissue Proteins/metabolism ; Neural Inhibition ; Presynaptic Terminals/drug effects/metabolism/*physiology ; R-SNARE Proteins ; Recombinant Fusion Proteins/metabolism ; Serotonin/pharmacology ; Synaptic Transmission/*drug effects ; Synaptosomal-Associated Protein 25 ; Syntaxin 1 ; beta-Adrenergic Receptor Kinases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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    PAPER CURRENT
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