Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse |
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| Affiliation: | 1. Department of Molecular Genetics The University of Texas Southwestern Medical Center Dallas, Texas 75235, USA;3. Department of Biochemistry The University of Texas Southwestern Medical Center Dallas, Texas 75235, USA;4. Howard Hughes Medical Institute The University of Texas Southwestern Medical Center Dallas, Texas 75235, USA;2. Molecular Neurobiology Laboratory and Howard Hughes Medical Institute The Salk Institute La Jolla, California 92037, USA;1. Department of Chemistry, University of Colorado Denver, Denver, Colorado;1. Institute of Physiology, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany;2. National Eye Institute, Section of Retinal Ganglion Cell Biology, National Institutes of Health, Bethesda, MD, USA;3. National Eye Institute, Genetic Engineering Facility, National Institutes of Health, Bethesda, MD, USA;4. Signaling Research Centers BIOSS and CIBSS, University of Freiburg, Schänzlestr. 18, 79104 Freiburg, Germany;5. Logopharm GmbH, Schlossstr. 14, 79232 March-Buchheim, Germany;1. Center for Neural Science, New York University, New York, NY 10003, USA;2. Department of Neuroscience and Physiology, Neuroscience Institute, New York University Langone Health, New York, NY 10016, USA;3. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA;4. Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, 3810 University Street, Montreal, QC, Canada;5. Neuroscience Program, Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine and the Fifth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510810, China;6. Sorbonne Université, INSERM U1127, UMR CNRS 7225, Institut du Cerveau (ICM), 47 bld de l’hôpital, 75013 Paris, France;3. Departments of Chemistry and University of Virginia, Charlottesville, Virginia 22904;5. Departments of Molecular Physiology and Biological Physics and University of Virginia, Charlottesville, Virginia 22904;4. Center for Membrane Biology, University of Virginia, Charlottesville, Virginia 22904 |
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| Abstract: | Mice carrying a mutation in the synaptotagmin I gene were generated by homologous recombination. Mutant mice are phenotypically normal as heterozygotes, but die within 48 hr after birth as homozygotes. Studies of hippocampal neurons cultured from homozygous mutant mice reveal that synaptic transmission is severely impaired. The synchronous, fast component of Ca2+-dependent neurotransmitter release is decreased, whereas asynchronous release processes, including spontaneous synaptic activity (miniature excitatory postsynaptic current frequency) and release triggered by hypertonic solution or α-latrotoxin, are unaffected. Our findings demonstrate that synaptotagmin I function is required for Ca2+-triggering of synchronous neurotransmitter release, but is not essential for asynchronous or Ca2+-independent release. We propose that synaptotagmin I is the major low affinity Ca2+ sensor mediating Ca2+ regulation of synchronous neurotransmitter release in hippocampal neurons. |
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