A shared vesicular carrier allows synaptic corelease of GABA and glycine
A shared vesicular carrier allows synaptic corelease of GABA and glycine
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DOI：
10.1016/j.neuron.2006.04.016
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发表时间：
2006-05-18
期刊：
影响因子：
16.2
通讯作者：
Rhee, Jeong-Seop
中科院分区：
文献类型：
--
作者：
Wojcik, Sonja M.;Katsurabayashi, Shutaro;Rhee, Jeong-Seop
由神经元表达的囊泡转运蛋白的类型被认为决定其神经递质表型。我们发现，囊泡抑制性氨基酸转运蛋白（Viaat，VGAT）的失活导致胚胎死亡，腹部缺陷称为脐膨出，腭裂。Viaat的丧失导致GABA能和甘氨酸能神经元中神经递质释放的急剧减少，表明甘氨酸能神经元不表达单独的囊泡甘氨酸转运蛋白。GABA能和甘氨酸能突触传递的这种丧失不会损害抑制性突触的发育或KCC 2的表达，KCC 2是已知对建立抑制性神经传递至关重要的K+-Cl-协同转运蛋白。在缺乏Viaat的情况下，GABA合成酶从突触前末端部分丢失。由于GABA和甘氨酸竞争囊泡摄取，这些数据表明Viaat与GABA合成酶密切相关，是指定GABA能神经元表型的关键因素。
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.