Enrichment of GABARAP relative to LC3 in the axonal initial segments of neurons.
Enrichment of GABARAP relative to LC3 in the axonal initial segments of neurons.
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DOI：
10.1371/journal.pone.0063568
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Uchiyama Y
中科院分区：
文献类型：
--
作者：
Koike M;Tanida I;Nanao T;Tada N;Iwata J;Ueno T;Kominami E;Uchiyama Y
GABAA受体相关蛋白(GABARAP)最初被鉴定为与GABAA受体相互作用的蛋白。虽然在正常情况下，GABARAP的同源物微管相关蛋白1轻链3已定位于神经元的树突和细胞体中，但GABARAP在神经元中的亚细胞分布尚不清楚。亚细胞分离表明，内源性GABARAP以GABARAP-I的形式定位于小鼠脑内富含微粒体和突触小泡的部分，这是一种未脂化的形式。为了研究GABARAP在神经元中的分布，我们产生了GFP-GABARAP转基因小鼠。这些转基因小鼠的免疫组织化学显示，GFP-GABARAP阳性信号广泛分布在包括海马区和小脑在内的不同脑区的神经元中。有趣的是，除胞体和树突外，GFP-GABARAP在海马锥体神经元和小脑浦肯野细胞的轴突起始段(AIS)也有较强的弥漫性和/或纤维性表达。相反，在这些神经元的AIS中只检测到少量的Lc3，而Lc3的弥漫性和/或纤维状染色主要出现在它们的胞体和树突中。这些结果表明，与LC3相比，GABARAP不仅富含这些海马区锥体神经元和小脑浦肯野细胞的胞体和树突，而且还富含AIS。
GABAA receptor-associated protein (GABARAP) was initially identified as a protein that interacts with GABAA receptor. Although LC3 (microtubule-associated protein 1 light chain 3), a GABARAP homolog, has been localized in the dendrites and cell bodies of neurons under normal conditions, the subcellular distribution of GABARAP in neurons remains unclear. Subcellular fractionation indicated that endogenous GABARAP was localized to the microsome-enriched and synaptic vesicle-enriched fractions of mouse brain as GABARAP-I, an unlipidated form. To investigate the distribution of GABARAP in neurons, we generated GFP-GABARAP transgenic mice. Immunohistochemistry in these transgenic mice showed that positive signals for GFP-GABARAP were widely distributed in neurons in various brain regions, including the hippocampus and cerebellum. Interestingly, intense diffuse and/or fibrillary expression of GFP-GABARAP was detected along the axonal initial segments (AIS) of hippocampal pyramidal neurons and cerebellar Purkinje cells, in addition to the cell bodies and dendrites of these neurons. In contrast, only slight amounts of LC3 were detected along the AIS of these neurons, while diffuse and/or fibrillary staining for LC3 was mainly detected in their cell bodies and dendrites. These results indicated that, compared with LC3, GABARAP is enriched in the AIS, in addition to the cell bodies and dendrites, of these hippocampal pyramidal neurons and cerebellar Purkinje cells.
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