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PMID: 15103023 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 18 ·2004-05-04 ·Pages 7158-63

Wojcik SM, Rhee JS, Herzog E, Sigler A, Jahn R, Takamori S, Brose N, Rosenmund C

Abstract

Quantal neurotransmitter release at excitatory synapses depends on glutamate import into synaptic vesicles by vesicular glutamate transporters (VGLUTs). Of the three known transporters, VGLUT1 and VGLUT2 are expressed prominently in the adult brain, but during the first two weeks of postnatal development, VGLUT2 expression predominates. Targeted deletion of VGLUT1 in mice causes lethality in the third postnatal week. Glutamatergic neurotransmission is drastically reduced in neurons from VGLUT1-deficient mice, with a specific reduction in quantal size. The remaining activity correlates with the expression of VGLUT2. This reduction in glutamatergic neurotransmission can be rescued and enhanced with overexpression of VGLUT1. These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission.

MeSH Terms
Amino Acid Transport Systems, Acidic/genetics,metabolism Animals Carrier Proteins/genetics,metabolism Electrophysiology Endocytosis/physiology Exocytosis/physiology Glutamic Acid/metabolism Hippocampus/growth & development,metabolism Membrane Transport Proteins Mice Mice, Knockout Neurons/metabolism Synapses/metabolism Vesicular Glutamate Transport Protein 1 Vesicular Glutamate Transport Protein 2 Vesicular Glutamate Transport Proteins Vesicular Transport Proteins
Chemicals
Amino Acid Transport Systems, Acidic Carrier Proteins Membrane Transport Proteins SLC17A8 protein, human Slc17a6 protein, mouse Slc17a7 protein, mouse Vesicular Glutamate Transport Protein 1 Vesicular Glutamate Transport Protein 2 Vesicular Glutamate Transport Proteins Vesicular Transport Proteins Glutamic Acid
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wojcik S M
Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, Hermann-Rein Strasse 3, D-37075 Göttingen, Germany.
Rhee J S
Herzog E
Sigler A
Jahn R
Takamori S
Brose N
Rosenmund C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0401764101
Published
2004-05-04
Epub
2004-00-21
Pages
7158-63
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC406482
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0401764101 PMC Full Text View journal details
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