Crowder, Kelly M.;
Gunther, Jane M.;
Jones, Theresa A.;
Hale, Brian D.;
Zhang, Hai Zhuan;
Peterson, Michael R.;
Scheller, Richard H.;
Chavkin, Charles;
Bajjalieh, Sandra M.
Abnormal Neurotransmission in Mice Lacking Synaptic Vesicle Protein 2A (SV2A)
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Media type:
E-Article
Title:
Abnormal Neurotransmission in Mice Lacking Synaptic Vesicle Protein 2A (SV2A)
Contributor:
Crowder, Kelly M.;
Gunther, Jane M.;
Jones, Theresa A.;
Hale, Brian D.;
Zhang, Hai Zhuan;
Peterson, Michael R.;
Scheller, Richard H.;
Chavkin, Charles;
Bajjalieh, Sandra M.
Published:
National Academy of Sciences of the United States of America, 1999
Published in:
Proceedings of the National Academy of Sciences of the United States of America, 96 (1999) 26, Seite 15268-15273
Description:
Synaptic vesicle protein 2 (SV2) is a membrane glycoprotein common to all synaptic and endocrine vesicles. Unlike many proteins involved in synaptic exocytosis, SV2 has no homology in yeast, indicating that it performs a function unique to secretion in higher eukaryotes. Although the structure and protein interactions of SV2 suggest multiple possible functions, its role in synaptic events remains unknown. To explore the function of SV2 in an in vivo context, we generated mice that do not express the primary SV2 isoform, SV2A, by using targeted gene disruption. Animals homozygous for the SV2A gene disruption appear normal at birth. However, they fail to grow, experience severe seizures, and die within 3 weeks, suggesting multiple neural and endocrine deficits. Electrophysiological studies of spontaneous inhibitory neurotransmission in the CA3 region of the hippocampus revealed that loss of SV2A leads to a reduction in action potential-dependent γ -aminobutyric acid (GABA)ergic neurotransmission. In contrast, action potential-independent neurotransmission was normal. Analyses of synapse ultrastructure suggest that altered neurotransmission is not caused by changes in synapse density or morphology. These findings demonstrate that SV2A is an essential protein and implicate it in the control of exocytosis.