Differential subcellular distribution of endosomal compartments and the dopamine transporter in dopaminergic neurons.
Differential subcellular distribution of endosomal compartments and the dopamine transporter in dopaminergic neurons.
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多巴胺能神经元中内体室和多巴胺转运蛋白的差异亚细胞分布。
DOI：
10.1016/j.mcn.2010.08.016
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发表时间：
2011-01
影响因子：
3.5
通讯作者：
Sorkin, Alexander
中科院分区：
文献类型：
--
作者：
Rao, Anjali;Simmons, Diana;Sorkin, Alexander
多巴胺转运蛋白（DAT）在多巴胺能神经元表面起清除细胞外DA的作用，DAT表面水平受内吞作用的调节。然而，内体溶酶体系统在多巴胺能神经元中没有很好的表征，内源性DAT的内吞运输研究很少。因此，我们用荧光显微镜分析了内吞区室的分布和DAT定位在培养的大鼠胚胎和出生后的神经元。早期Rab5和EEA.1内体主要存在于神经元的体树突区域，而含有再循环标记物的内体主要存在于轴突中。在轴突中，DAT主要位于再循环内体和质膜中，而在细胞体和树突中，DAT在早期、晚期和再循环内体隔室中被检测到。成年大鼠纹状体突触体的亚细胞分级分离表明，DAT富含含有质膜和再循环内体的组分。这种模式的DAT分布没有改变后，激活蛋白激酶C在出生后的DA神经元。总之，我们的数据表明，轴突DAT主要穿梭于质膜和再循环内体之间，而在神经元的体树突区域，DAT通过所有传统的内体途径进行运输。
Dopamine (DA) transporter (DAT) functions at the surface of dopaminergic neurons to clear extracellular DA. DAT surface levels are regulated by endocytosis. However, the endosomelysosome system is not well characterized in dopaminergic neurons and the endocytic trafficking of endogenous DAT is poorly studied. Hence we analyzed the distribution of endocytic compartments and DAT localization in cultured rat embryonic and postnatal neurons using fluorescence microscopy. Early Rab5 and EEA.1 containing endosomes were mostly found in somatodendritic regions of neurons, whereas endosomes containing recycling markers were primarily found in axons. In axons, DAT was located mainly in recycling endosomes and plasma membrane whereas in cell bodies and dendrites DAT was detected in early, late and recycling endosomal compartments. Subcellular fractionation of adult rat striatal synaptosomes demonstrated that DAT is enriched in fractions containing plasma membrane and recycling endosomes. This pattern of DAT distribution was not altered upon activation of protein kinase C in postnatal DA neurons. Altogether, our data suggest that axonal DAT mainly shuttles between the plasma membrane and recycling endosomes, whereas in the somatodendritic region of neurons DAT traffics through all conventional endosomal pathways.
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影响因子：
25
作者：
Holton, KL;Loder, MK;Melikian, HE
通讯作者：
Melikian, HE
影响因子：
4.8
作者：
Loder, MK;Melikian, HE
通讯作者：
Melikian, HE
影响因子：
5.3
作者：
CILIAX, BJ;HEILMAN, C;LEVEY, AI
通讯作者：
LEVEY, AI
影响因子：
5.3
作者：
Egana, Loreto A.;Cuevas, Rolando A.;Torres, Gonzalo E.
通讯作者：
Torres, Gonzalo E.
影响因子：
3.5
作者：
Mani, Meera;Ryan, Timothy A.
通讯作者：
Ryan, Timothy A.