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PMID: 22036572 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release.

Cell ·Vol. 147 ·No. 3 ·2011-10-28 ·Pages 666-77

Yao J, Gaffaney JD, Kwon SE, Chapman ER

Abstract

Synaptic transmission involves a fast synchronous phase and a slower asynchronous phase of neurotransmitter release that are regulated by distinct Ca(2+) sensors. Though the Ca(2+) sensor for rapid exocytosis, synaptotagmin I, has been studied in depth, the sensor for asynchronous release remains unknown. In a screen for neuronal Ca(2+) sensors that respond to changes in [Ca(2+)] with markedly slower kinetics than synaptotagmin I, we observed that Doc2--another Ca(2+), SNARE, and lipid-binding protein--operates on timescales consistent with asynchronous release. Moreover, up- and downregulation of Doc2 expression levels in hippocampal neurons increased or decreased, respectively, the slow phase of synaptic transmission. Synchronous release, when triggered by single action potentials, was unaffected by manipulation of Doc2 but was enhanced during repetitive stimulation in Doc2 knockdown neurons, potentially due to greater vesicle availability. In summary, we propose that Doc2 is a Ca(2+) sensor that is kinetically tuned to regulate asynchronous neurotransmitter release.

MeSH Terms
Action Potentials Animals Calcium/metabolism Calcium-Binding Proteins/metabolism Cells, Cultured Gene Knockdown Techniques Hippocampus/cytology,metabolism Humans Lipid Metabolism Mice Nerve Tissue Proteins/metabolism Neurons/metabolism Neurotransmitter Agents/metabolism Rats SNARE Proteins/metabolism Synaptic Transmission Synaptic Vesicles/metabolism Synaptotagmin I/genetics,metabolism
Chemicals
Calcium-Binding Proteins DOC2A protein, human DOC2B protein, human Nerve Tissue Proteins Neurotransmitter Agents SNARE Proteins Synaptotagmin I Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yao Jun
Howard Hughes Medical Institute and Department of Neuroscience, University of Wisconsin, Madison, WI 53706, USA.
Gaffaney Jon D
Kwon Sung E
Chapman Edwin R
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2011.09.046
Published
2011-10-28
Pages
666-77
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC3220409
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIMH NIH HHS · R01 MH061876 · United States
NIMH NIH HHS · R01 MH061876-09 · United States
NIMH NIH HHS · MH 61876 · United States
Corrections
CommentIn
PMID: 22036557
External Links
PubMed source DOI: 10.1016/j.cell.2011.09.046 PMC Full Text View journal details
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