Expression and immunolocalization of the plasma membrane monoamine transporter in the brain

Expression and immunolocalization of the plasma membrane monoamine transporter in the brain
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DOI:
10.1016/j.neuroscience.2007.01.072
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发表时间:
2007-05-25
期刊:
影响因子:
3.3
通讯作者:
Wang, J.
Wang, J.
中科院分区:
医学3区
文献类型:
--
作者:
Dahlin, A.;Xia, L.;Wang, J.

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高亲和力单胺转运蛋白通过突触重摄取释放的神经递质有效地终止神经传递。我们最近克隆和表征了一种新的低亲和力,高容量质膜单胺转运蛋白(PMAT),它在人脑中强烈表达,并有效地转运5-HT和多巴胺(DA)。为了了解PMAT的生理功能及其在单胺能通路中的相关性,我们从小鼠脑中克隆了PMAT同源物,证明了其转运5-HT和DA的能力,并通过逆转录聚合酶链反应,非放射性原位杂交,免疫组织化学方法。我们的研究结果表明,mPMAT mRNA和蛋白在小鼠脑中广泛表达,特别是丰富的前脑皮层,嗅结节,海马,小脑和脉络丛上皮细胞。双重免疫荧光组织化学与已建立的表型标记微管相关蛋白(MAP 2)和胶质细胞酸性蛋白(GFAP)显示,mPMAT是在神经元细胞中表达,但不是在星形胶质细胞。mPMAT与高亲和力5-HT转运蛋白(SERT)和多巴胺转运蛋白(DAT)在许多脑区共表达,但也发现在某些部位接受单胺神经支配,但缺乏显着的SERT或DAT的表达。这些研究结果表明,mPMAT是一种广泛分布的,神经元表达的转运蛋白,这可能支持在某些条件下的5-HT和DA摄取的作用。(c)2007年IBRO。由爱思唯尔有限公司出版。保留所有权利。
High affinity monoamine transporters efficiently terminate neurotransmission through synaptic reuptake of released neurotransmitter. We recently cloned and characterized a novel low-affinity, high capacity plasma membrane monoamine transporter (PMAT) that is strongly expressed in the human brain and efficiently transports 5-HT and dopamine (DA). In efforts to understand the physiological function of PMAT and its relevance in monoaminergic pathways, we cloned the PMAT homolog from the mouse brain, demonstrated its capability for transporting 5-HT and DA, and determined the regional and cellular localization of mouse plasma membrane monoamine transporter (mPMAT) in adult mouse brain by reverse-transcription polymerase chain reaction, non-radioactive in situ hybridization, and immunohistochemical methods. Our results showed that mPMAT mRNA and protein are broadly expressed in the mouse brain and are particularly abundant in forebrain cortex, olfactory tubercle, hippocampus, cerebellum and epithelial cells of the choroid plexus. Dual-immunofluorescence histochemistry with established phenotypic markers microtubule-associated protein (MAP2) and glial fibrillary acidic protein (GFAP) revealed that mPMAT is expressed in neuronal cells but not in astrocytes. mPMAT is co-expressed in many brain regions with the high affinity 5-HT transporter (SERT) and the dopamine transporter (DAT), but is also found in certain sites that receive monoamine innervation but lack significant expression of SERT or DAT. These findings suggest that mPMAT is a widely distributed, neuronally-expressed transporter, which may support the role of 5-HT and DA uptake under certain conditions. (c) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.