A shared vesicular carrier allows synaptic corelease of GABA and glycine.
The type of vesicular transporter expressed by a neuron is thought to determine its neurotransmitter phenotype. We show that inactivation of the vesicular inhibitory amino acid transporter (Viaat, VGAT) leads to embryonic lethality, an abdominal defect known as omphalocele, and a cleft palate. Loss of Viaat causes a drastic reduction of neurotransmitter release in both GABAergic and glycinergic neurons, indicating that glycinergic neurons do not express a separate vesicular glycine transporter. This loss of GABAergic and glycinergic synaptic transmission does not impair the development of inhibitory synapses or the expression of KCC2, the K+ -Cl- cotransporter known to be essential for the establishment of inhibitory neurotransmission. In the absence of Viaat, GABA-synthesizing enzymes are partially lost from presynaptic terminals. Since GABA and glycine compete for vesicular uptake, these data point to a close association of Viaat with GABA-synthesizing enzymes as a key factor in specifying GABAergic neuronal phenotypes.
Wojcik
Sonja M
SM
Department of Molecular Neurobiology, Max-Planck-Institute of Experimental Medicine, D-37075 Göttingen, Germany. wojcik@em.mpg.de
Katsurabayashi
Shutaro
S
Guillemin
Isabelle
I
Friauf
Eckhard
E
Rosenmund
Christian
C
Brose
Nils
N
Rhee
Jeong-Seop
JS
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D018079:Receptors, GABA / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D027981:Symporters / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000172:deficiency*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000096922:K Cl- Cotransporters
D005968:Glutamate Decarboxylase; D005998:Glycine; D007527:Isoenzymes; D018079:Receptors, GABA; D018009:Receptors, Glycine; D027981:Symporters; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C492244:Viaat protein, mouse; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2