Cited by 1,483Cellular transport and secretionNeuroscience and Neuropharmacology ResearchCalcium signaling and nucleotide metabolism

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Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse

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Geppert, Martin, Goda, Yukiko, Hammer, Robert E., Li, Cai, Rosahl, Thomas W., Stevens, Charles F., Südhof, Thomas C.·1994·Cell

DOI 10.1016/0092-8674(94)90556-8

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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 Ca(2+)-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 alpha-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 Ca(2+)-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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Authors: Geppert, M., Goda, Y., Hammer, R. E., Li, C., Rosahl, T. W., Stevens, C. F., & Südhof, T. C.
Affiliations: The University of Texas Southwestern Medical Center (US)
Salk Institute for Biological Studies (US)
Howard Hughes Medical Institute (US)
ORCID: Goda, Yukiko
Rosahl, Thomas W.
Stevens, Charles F.
Südhof, Thomas C.
Venue: Cell
Publisher: Elsevier BV
Published: 1994-11
Volume: 79
Issue: 4
Pages: 717-727
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(94)90556-8
OpenAlex: W2165302477
Cited by: 1,483
References: 45
Citations by year: 2026: 17 · 2025: 24 · 2024: 34 · 2023: 36 · 2022: 41 · 2021: 42 · 2020: 47 · 2019: 49 · 2018: 43 · 2017: 41 · 2016: 31 · 2015: 41 · 2014: 51 · 2013: 33 · 2012: 59
FWCI: 20.67
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Deutsche Forschungsgemeinschaft
National Institutes of Health (5r01ns012961-22)
National Institute of Neurological Disorders and Stroke (R0 NS 12961-17)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords: synaptotagmin-1, calcium sensor, asynchronous release, calcium-independent release, hippocampal neurons, synaptic transmission, mouse mutants, alpha-latrotoxin, spontaneous synaptic activity
MeSH terms: Animals, Animals, Newborn, Base Sequence, Brain, Calcium, Calcium-Binding Proteins, Exons, Hippocampus, Homozygote, Hypertonic Solutions, Membrane Glycoproteins, Mice, Neurologic Mutants, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Reference Values, Spider Venoms, Synapses, Restriction Mapping, Polymerase Chain Reaction, Mutagenesis, DNA Primers, Neurotransmitter Agents, Synaptotagmins, Synaptotagmin I, Mice

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Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse

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