Structure, function and brain localization of neurotransmitter transporters.
Structure, function and brain localization of neurotransmitter transporters.
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神经递质转运蛋白的结构、功能和大脑定位。
DOI：
--
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发表时间：
1994
影响因子：
2.8
通讯作者：
Nathan Nelson
中科院分区：
文献类型：
--
作者：
F. Jursky;Shigehiko Tamura;Akiko Tamura;S. Mandiyan;Hannah Nelson;Nathan Nelson
我们研究了小鼠和大鼠大脑中四种不同的编码 GABA 转运蛋白的 cDNA 和三种不同的编码甘氨酸转运蛋白的 cDNA。两种甘氨酸转运蛋白（GLYT1a 和 GLYT1b）的基因组克隆表明，它们源自单个基因的差异剪接。第三种甘氨酸转运蛋白 (GLYT2) 由单独的基因编码。针对其中七种神经递质转运蛋白产生了抗体，并研究了它们在小鼠大脑中的细胞化学定位。一般来说，我们观察到神经元和神经胶质转运蛋白的经典分离存在偏差。似乎每种神经递质转运蛋白都存在于大脑的特定位置，并且在非常特定的区域以不同的方式表达。例如，GABA 转运蛋白 GAT4（也转运 β-丙氨酸）定位于神经元。然而，GABA 特异性的 GAT1 不仅定位于神经元，还定位于神经胶质细胞。最近发现的甘氨酸转运蛋白 GLYT2 引起了人们的特别兴趣，因为它的 N 末端非常延伸，含有多个潜在的磷酸化位点，从而偏离了一般结构。小鼠大脑冰冻切片的蛋白质印迹分析和免疫细胞化学显示，GLYT2 分布存在明显的尾侧-喙侧梯度，在脊髓和脑干中大量积累，在小脑中较少。它的分布通常是神经元的，并且存在于具有静脉曲张的过程中。我们获得的模式与之前从士的宁结合研究中观察到的模式之间观察到的相关性。结果表明，GLYT2 参与后脑经典抑制系统甘氨酸神经传递的终止。四种不同 GABA 转运蛋白的可用性使得寻找神经递质转运蛋白上的特定结合位点成为可能。一项广泛的定点诱变计划使我们发现了 GABA 转运蛋白上潜在的神经递质结合位点。
We studied four different cDNAs encoding GABA transporters and three different cDNAs encoding glycine transporters in mouse and rat brains. A genomic clone of two of the glycine transporters (GLYT1a and GLYT1b) revealed that they derive from differential splicing of a single gene. The third glycine transporter (GLYT2) is encoded by a separate gene. Antibodies were raised against seven of these neurotransmitter transporters and their cytochemical localization in the mouse brain was studied. In general, we observed a deviation from the classical separation of neuronal and glial transporters. It seems that each of the neurotransmitter transporters is present in specific places in the brain and is expressed in a different way in very specific areas. For example, the GABA transporter GAT4, which also transports beta-alanine, was localized to neurons. However, GAT1, which is specific for GABA, was localized not only to neurons but also to glial cells. The recently discovered glycine transporter GLYT2 was of particular interest because of its deviation from the general structure by a very extended N terminus containing multiple potential phosphorylation sites. Western analysis and immunocytochemistry in frozen sections of mouse brain demonstrated a clear caudal-rostral gradient of GLYT2 distribution, with massive accumulation in the spinal cord and brainstem and less in the cerebellum. Its distribution is typically neuronal and it is present in processes with varicosities. A correlation as observed between the pattern we obtained and that observed previously from strychnine binding studies. The results indicate that GLYT2 is involved in the termination of glycine neurotransmission at the classical inhibitory system in the hindbrain. The availability of four different GABA transporters made it possible to look for specific binding sites upon the neurotransmitter transporters. An extensive program of site-directed mutagenesis led us to identify a potential neurotransmitter binding site on the GABA transporters.
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DOI：
10.1016/s0021-9258(18)53681-4
发表时间：
1993-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
S. Pantanowitz;A. Bendahan;B. Kanner
通讯作者：
S. Pantanowitz;A. Bendahan;B. Kanner
DOI：
10.1073/pnas.89.15.7189
发表时间：
1992-08-01
影响因子：
11.1
作者：
GUASTELLA, J;BRECHA, N;DAVIDSON, N
通讯作者：
DAVIDSON, N
影响因子：
56.9
作者：
GUASTELLA, J;NELSON, N;KANNER, BI
通讯作者：
KANNER, BI
轴突 γ-氨基丁酸转运蛋白 GAT-1 被分选至极化上皮细胞的顶膜。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Pietrini,G;Suh,YJ;Edelmann,L;Rudnick,G;Caplan,MJ
通讯作者：
Caplan,MJ
HepG2 (Glut1) 葡萄糖转运蛋白的色氨酸 388 和色氨酸 412 处的氨基酸取代会抑制爪蟾卵母细胞中的转运活性和质膜靶向。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Garcia,JC;Strube,M;Leingang,K;Keller,K;Mueckler,MM
通讯作者：
Mueckler,MM