Identification and characterization of ε-sarcoglycans in the central nervous system
Identification and characterization of ε-sarcoglycans in the central nervous system
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DOI：
10.1016/j.molbrainres.2004.01.012
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发表时间：
2004-06-18
期刊：
影响因子：
--
通讯作者：
Imamura, M
中科院分区：
文献类型：
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作者：
Nishiyama, A;Endo, T;Imamura, M
α、β、γ 和 δ 肌聚糖 (SG) 是肌营养不良蛋白相关蛋白 (DAP) 复合物的跨膜糖蛋白成分，对于横纹肌细胞膜的稳定性至关重要。 epsilon-SG 被发现是 α-SG 的同源物，但与其他 SG 成员不同，它广泛表达于各种组织以及横纹肌中。此外，epsilon-SG基因的突变会导致肌阵挛-肌张力障碍，表明epsilon-SG对于中枢神经系统功能的重要性。为了深入了解 epsilon-SG 的作用，研究了其在小鼠组织，特别是小鼠大脑中的表达和亚细胞分布。逆转录聚合酶链式反应分析显示小鼠大脑中 epsilon-SG 转录物有四种剪接变体，其中两种是主要转录物形式。一种是包含外显子8 (epsilon-SG1) 的常规形式，另一种是排除外显子8 但包含先前未知的外显子11b (epsilon-SG2) 的新型形式。使用各种小鼠组织进行的免疫印迹分析表明 epsilon-SG1 具有广泛的表达模式，但 epsilon-SG2 仅在大脑中表达。因此，两种 epsilon-SG 亚型共存于大脑的各个区域。此外，通过免疫组织化学分析在神经元细胞中发现了这些亚型。然而，脑匀浆的亚细胞分级分离表明，epsilon-SG1 和 epsilon-SG2 分别在突触后膜组分和突触前膜组分中相对富集。这些结果表明两种 epsilon-SG 亚型可能在中枢神经系统的突触功能中发挥不同的作用。 (C) 2004 Elsevier B.V 保留所有权利。
alpha-,beta-, gamma-, and delta-Sarcoglycans (SGs) are transmembrane glycoprotein components of the dystrophin-associated protein (DAP) complex, which is critical for the stability of the striated muscle cell membrane. epsilon-SG was found as a homologue of alpha-SG, but unlike other SG members, it is ubiquitously expressed in various tissues as well as in striated muscle. Moreover, mutations in the epsilon-SG gene cause myoclonus-dystonia, indicating the importance of epsilon-SG for the function in the central nervous system. To gain insight into the role of epsilon-SG, its expression and subcellular distribution in mouse tissues and especially in the mouse brain were investigated. Analysis by reverse transcription-polymerase chain reaction showed four splice variants of epsilon-SG transcripts in the mouse brain, two of which are major transcript forms. One is a conventional form including exon 8 (epsilon-SG1), and the other is a novel form excluding exon 8 but including a previously unknown exon, 11b (epsilon-SG2). Immunoblot analysis using various mouse tissues indicated a broad expression pattern for epsilon-SG1, but epsilon-SG2 was expressed exclusively in the brain. Therefore, both epsilon-SG isoforms coexist in various regions of the brain. Furthermore, these isoforms were found in neuronal cells using immunohistochemical analysis. Subcellular fractionation of brain homogenates, however, indicated that epsilon-SG1 and epsilon-SG2 are relatively enriched in post- and pre-synaptic membrane fractions, respectively. These results suggest that the two epsilon-SG isoforms might play different roles in synaptic functions of the central nervous system. (C) 2004 Elsevier B.V All rights reserved.