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Cited by 313Cellular transport and secretionNeuroscience and Neuropharmacology ResearchCalcium signaling and nucleotide metabolism

Doc2b Is a High-Affinity Ca 2+ Sensor for Spontaneous Neurotransmitter Release

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Groffen, Alexander J., Martens, Sascha, Arazola, Rocío Díez, Cornelisse, L. Niels, Lozovaya, Natalia, de Jong, Arthur P. H., Goriounova, Natalia A., Habets, Ron L. P. +5 more·2010·Science
DOI 10.1126/science.1183765PMC PMC2846320
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Abstract

“Spontaneous” Release Trigger: Synaptic vesicle release occurs in different phases that can be tightly coupled to action potentials (synchronous), immediately following action potentials (asynchronous), or as stochastic events not triggered by action potentials (spontaneous). The vesicle protein synaptotagmin is thought to act as the Ca 2+ sensor in the synchronous phase, but for the other two phases, Ca 2+ sensors have not been identified. Groffen et al. (p. 1614 , published online 11 February) now show that cytoplasmic proteins known as Doc2 (double C2 domain) proteins are required for spontaneous release. Doc2 proteins promote membrane fusion in response to exceptionally low increases in Ca 2+ , and are several orders of magnitude more sensitive to Ca 2+ than synaptotagmin. Doc2 and synaptotagmin compete for SNARE-complex binding during membrane fusion. A mutation that abolishes the Ca 2+ dependence of Doc2b also abolishes the Ca 2+ dependence of spontaneous release. Thus, Doc2 is a high-affinity Ca 2+ sensor for spontaneous release that competes with synaptotagmin for SNARE complex binding.

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Authors
Groffen, A. J., Martens, S., Arazola, R. D., Cornelisse, L. N., Lozovaya, N., de Jong, A. P. H., Goriounova, N. A., Habets, R. L. P., Takai, Y., Borst, J. G., Brose, N., McMahon, H. T., & Verhage, M.
Affiliations
  • Amsterdam Neuroscience (NL)
  • MRC Laboratory of Molecular Biology (GB)
  • Bogomoletz Institute of Physiology (UA)
  • Department of Functional Genomics, CNCR, Neuroscience Campus Amsterdam, VU University and VU Medical Center, Amsterdam, 1081 HV, Netherlands.
  • Erasmus MC (NL)
  • Kobe University (JP)
Corresponding author
  • Groffen, Alexander J.
  • Martens, Sascha
  • Habets, Ron L. P.
  • McMahon, Harvey T.
  • Verhage, Matthijs
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2010-03-26
Volume
327
Issue
5973
Pages
1614-1618
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.1183765
PMC
PMC2846320
OpenAlex
W2041423137
Cited by
313
References
2
Citations by year
2026: 8 · 2025: 11 · 2024: 13 · 2023: 16 · 2022: 16 · 2021: 16 · 2020: 14 · 2019: 19 · 2018: 15 · 2017: 16 · 2016: 14 · 2015: 22 · 2014: 31 · 2013: 26 · 2012: 32
FWCI
14.26
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • VU Research Portal (publishedVersion)
  • PubMed Central (acceptedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • GRO (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • RePub (Erasmus University Rotterdam) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
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
DOC2B, C2 domain proteins, calcium sensor, spontaneous neurotransmitter release, synaptic vesicle fusion, synaptotagmin-1, SNARE complex, synchronous release, asynchronous release, calcium sensitivity
MeSH terms
Action Potentials, Animals, Binding Sites, Calcium, Calcium-Binding Proteins, Cells, Cultured, Hippocampus, Membrane Fusion, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Purkinje Cells, Synaptic Vesicles, Protein Structure, Tertiary, Mice, Knockout, Neurotransmitter Agents, Patch-Clamp Techniques, Excitatory Postsynaptic Potentials, Mutant Proteins, SNARE Proteins, Synaptotagmin I, Mice, Rats, Inhibitory Postsynaptic Potentials

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