An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size.
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.
Wojcik
S M
SM
Department of Molecular Neurobiology, Max Planck Institute for Experimental Medicine, Hermann-Rein Strasse 3, D-37075 Göttingen, Germany.
Rhee
J S
JS
Herzog
E
E
Sigler
A
A
Jahn
R
R
Takamori
S
S
Brose
N
N
Rosenmund
C
C
D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050496:Vesicular Glutamate Transport Proteins; D033921:Vesicular Transport Proteins
D026922:Amino Acid Transport Systems, Acidic; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C460879:SLC17A8 protein, human; C493477:Slc17a6 protein, mouse; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050496:Vesicular Glutamate Transport Proteins; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid