Involvement of CD45 in central nervous system myelination
Involvement of CD45 in central nervous system myelination
复制标题
DOI：
10.1016/j.neulet.2004.12.066
复制
发表时间：
2005-05-06
影响因子：
2.5
通讯作者：
Aiso, S
中科院分区：
文献类型：
--
作者：
Nakahara, J;Seiwa, C;Aiso, S
髓磷脂是一种多层膜脂质绝缘体周围的轴突，使神经冲动的快速传导。在中枢神经系统（CNS）中，髓鞘由少突胶质细胞产生。在发育过程中，形态学上未成熟的少突胶质前体细胞（OPCs）在出生后不久分化成髓鞘形成的少突胶质细胞之前由神经干细胞产生。Fyn酪氨酸激酶（Fyn）已被证明在OPC分化过程中发挥核心作用，包括诱导细胞的形态学变化和启动髓鞘碱性蛋白（MBP）的表达，髓鞘碱性蛋白是髓鞘致密化所需的主要结构蛋白。最近，我们已经表明，通过免疫球蛋白Fc受体（FcR γ）的γ链的信号转导诱导Fyn-MBP级联反应，并促进OPCs的形态分化。然而，在此级联反应中负责Fyn酪氨酸激酶活性正调控的蛋白酪氨酸磷酸酶仍然未知。在这里，我们报告，蛋白酪氨酸磷酸酶，CD 45，参与这一过程。Fyn与来自体外分化的野生型OPCs的CD 45共免疫沉淀，而CD 45缺陷的OPCs未能分化。此外，在体内CD 45缺陷小鼠中观察到髓鞘形成障碍。我们的研究结果表明，CD 45是一个关键的磷酸酶参与OPC分化，并提供了一个初步的解释，以前报道的CD 45突变观察到的一些多发性硬化症（MS）患者。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Myelin is a multi-layered membranous lipid insulator surrounding axons that allows the rapid conduction of neuronal impulses. In the central nervous system (CNS), myelin is produced by oligodendrocytes. During development, morphologically immature oligodendrocyte precursor cells (OPCs) arise from neural stem cells before differentiating into myelinating oligodendrocytes shortly after birth. Fyn tyrosine kinase (Fyn) has been shown to play a central role during OPC differentiation, including inducing morphological changes in the cells and initiating the expression of myelin basic protein (MBP), a major structural protein required for the compaction of myelin sheaths. Recently, we have shown that signaling via the gamma chain of immunoglobulin Fc receptors (FcR gamma) induces the Fyn-MBP cascade and promotes the morphological differentiation of OPCs. The protein tyrosine phosphatases that are responsible for the positive regulation of Fyn tyrosine kinase activity during this cascade, however, remained unknown. Here we report that a protein tyrosine phosphatase, CD45, is involved in this process. Fyn co-immunoprecipitated with CD45 from differentiating wild-type OPCs in vitro, while CD45-deficient OPCs failed to differentiate. Additionally, dysmyelination was observed in CD45-deficient mice in vivo. Our findings suggest that CD45 is a key phosphatase involved in OPC differentiation and provide a preliminary explanation for the previously reported CD45 mutations observed in some multiple sclerosis (MS) patients. (c) 2005 Elsevier Ireland Ltd. All rights reserved.