Developmental and spatial expression pattern of α-taxilin in the rat central nervous system

Developmental and spatial expression pattern of α-taxilin in the rat central nervous system
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DOI:
10.1002/cne.21817
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发表时间:
2008-11-01
影响因子:
2.5
通讯作者:
Ueda, Shuichi
Ueda, Shuichi
中科院分区:
医学3区
文献类型:
--
作者:
Sakakibara, Shin-Ichi;Nakadate, Kazuhiko;Ueda, Shuichi

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α - taxilin已被确定为syntaxin家族成员的结合伙伴,因此被认为在syntaxin介导的细胞内囊泡运输中起作用。然而,缺乏关于α -taxilin的细胞和亚细胞定位的详细信息阻碍了对该蛋白作用的理解。在本研究中,我们用特异性抗体表征了大鼠中枢神经系统中表达α -taxilin的细胞。在胚胎发育过程中,α -taxilin在巢蛋白阳性的神经干细胞中显著表达。随着中枢神经系统的发育,α -taxilin的表达水平迅速下调。在出生后中枢神经系统中,a-taxilin的表达几乎局限于神经元谱系,在脑干核和脊髓内的运动神经元以及中脑三叉神经核内的初级感觉神经元中表达水平最高。在细胞水平上,α -taxilin优先位于细胞内和树突近端具有虎状或球状形态的Nissl物质样结构中,但在终末被排除在外。碘化丙啶联合染色表明,a-taxilin分布与RNA种类丰富的细胞质室重叠,提示a-taxilin与神经元中活跃翻译的核糖体或多体密切相关。与此一致,最近的一项研究表明,α -taxilin与新生多肽相关复合物(α NAC)优先结合,α NAC是真核细胞中核糖体出口通道的动态组成部分。综上所述,这些发现表明a-taxilin通过调节nac介导的翻译机制和/或胞体中syntaxin介导的囊泡运输,在神经元的产生和维持中发挥了多种作用。
alpha-Taxilin has been identified as a binding partner of syntaxin family members and thus has been proposed to function in syntaxin-mediated intracellular vesicle trafficking. However, the lack of detailed information concerning the cellular and subcellular localization of alpha-taxilin impedes an understanding of the role of this protein. In the present study, we characterized alpha-taxilin-expressing cells in the rat CNS with a specific antibody. During embryonic development, alpha-taxilin was prominently expressed in nestin-positive neural stem cells in vivo and in vitro. As CNS development proceeded, the alpha-taxilin expression level was rapidly down-regulated. In the postnatal CNS, a-taxilin expression was almost confined to the neuronal lineage, with the highest levels of expression in motor neurons within the brainstem nuclei and spinal cord and in primary sensory neurons in mesencephalic trigeminal nucleus. At the cellular level, alpha-taxilin was preferentially located in Nissl substance-like structures with a tigroid or globular morphology within the soma and proximal to dendrites, but it was excluded from terminals. Combined staining with propidium iodide demonstrated that a-taxilin distribution overlapped with the cytoplasmic compartment enriched in RNA species, suggesting a close association of a-taxilin with actively translating ribosomes or polysomes in neurons. In agreement with this, a recent study indicated the preferential binding of alpha-taxilin to the nascent polypeptide-associated complex (alpha NAC), a dynamic component of the ribosomal exit tunnel in eukaryotic cells. Taken together, these findings suggest that a-taxilin plays multiple roles in the generation and maintenance of neurons through modulation of the NAC-mediated translational machinary and/or the syntaxin-mediated vesicle traffic in the soma.