Biochemical characterization of MLC1 protein in astrocytes and its association with the dystrophin-glycoprotein complex
Biochemical characterization of MLC1 protein in astrocytes and its association with the dystrophin-glycoprotein complex
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DOI：
10.1016/j.mcn.2007.11.003
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发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Aloisi, Francesca
中科院分区：
文献类型：
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作者：
Ambrosini, Elena;Serafini, Barbara;Aloisi, Francesca
MLC1基因突变与巨脑白质脑病伴皮质下囊肿（MLC）有关，MLC是一种罕见的儿童神经系统疾病。MLC1基因编码一种功能未知的膜蛋白（MLC1），主要表达于星形胶质细胞。利用新开发的抗人MLC1多克隆抗体，我们研究了MLC1在培养的星形胶质细胞和脑组织中的生化特性和定位，并寻找MLC1与肌营养不良蛋白-糖蛋白复合物（DGC）蛋白之间关系的证据。培养的星形胶质细胞表达两种MLC1成分，具有不同的溶解特性和亚细胞分布。最重要的是，我们发现MLC1的膜相关成分（60-64 kDa）与糖异常蛋白、syntrophin和caveolin-1一起定位于星形胶质细胞脂筏中，并与整个大鼠脑组织中的DGC共同分离。在人脑中，MLC1蛋白在星形胶质细胞过程和室管膜细胞中表达，在那里它与糖代谢障碍和syntrophin共定位。这些数据表明DGC可能参与了星形胶质细胞膜中MLC1蛋白的组织和功能。(c) 2007爱思唯尔公司版权所有。
MLC1 gene mutations have been associated with megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare neurologic disorder in children. The MLC1 gene encodes a membrane protein (MLC1) with unknown function which is mainly expressed in astrocytes. Using a newly developed anti-human MLC1 polyclonal antibody, we have investigated the biochemical properties and localization of MLC1 in cultured astrocytes and brain tissue and searched for evidence of a relationship between MLC1 and proteins of the dystrophin-glycoprotein complex (DGC). Cultured astrocytes express two MLC1 components showing different solubilisation properties and subcellular distribution. Most importantly, we show that the membrane-associated component of MLC1 (60-64 kDa) localizes in astrocytic lipid rafts together with dystroglycan, syntrophin and caveolin-1, and co-fractionates with the DGC in whole rat brain tissue. In the human brain, MLC1 protein is expressed in astrocyte processes and ependymal cells, where it colocalizes with dystroglycan and syntrophin. These data indicate that the DGC may be involved in the organization and function of the MLC1 protein in astrocyte membranes. (c) 2007 Elsevier Inc. All rights reserved.