Wojcik Sonja M, Katsurabayashi Shutaro, Guillemin Isabelle, Friauf Eckhard, Rosenmund Christian, Brose Nils, Rhee Jeong-Seop
Department of Molecular Neurobiology, Max-Planck-Institute of Experimental Medicine, D-37075 Göttingen, Germany.
Neuron. 2006 May 18;50(4):575-87. doi: 10.1016/j.neuron.2006.04.016.
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.
神经元所表达的囊泡转运体类型被认为决定了其神经递质表型。我们发现，囊泡抑制性氨基酸转运体（Viaat，VGAT）失活会导致胚胎致死、一种名为脐膨出的腹部缺陷以及腭裂。Viaat的缺失导致GABA能和甘氨酸能神经元中神经递质释放急剧减少，这表明甘氨酸能神经元不表达单独的囊泡甘氨酸转运体。GABA能和甘氨酸能突触传递的丧失并不损害抑制性突触的发育或KCC2的表达，KCC2是已知对抑制性神经传递的建立至关重要的K⁺-Cl⁻共转运体。在没有Viaat的情况下，GABA合成酶从突触前终末部分丢失。由于GABA和甘氨酸竞争囊泡摄取，这些数据表明Viaat与GABA合成酶的紧密关联是确定GABA能神经元表型的关键因素。
