Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein.

Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein.
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DOI:
10.1083/jcb.200411047
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发表时间:
2005-08-15
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Braun PE
Braun PE
中科院分区:
其他
文献类型:
--
作者:
Lee J;Gravel M;Zhang R;Thibault P;Braun PE

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少突胶质细胞(OL)延伸由微管(MT)和微丝支持的树枝状突起。人们对髓鞘形成过程中调节细胞骨架并与之相互作用的蛋白质知之甚少。一些证据表明,2‘,3’-环核苷酸3‘-磷酸二酯酶(CNP)在OLS的过程形成中起着重要作用。在这项研究中,我们报告了微管蛋白是一种主要的CNP相互作用蛋白。在体外,与MTS相比,CNP优先与微管蛋白二聚体结合,并通过与微管蛋白共聚来诱导MT组装。CNP过表达诱导神经胶质细胞和非胶质细胞形态发生显著变化,导致MT和F-肌动蛋白重组和分支突起的形成。这些形态效应归因于CNP MT组装活性;随着功能缺失突变体的表达,分支突起的形成要么大大减少,要么被取消。因此,培养的来自CNP缺乏的小鼠的OL以较少的枝状突起延伸出较小的突起。我们认为,CNP是细胞骨架机制的一个重要组成部分,它指导着OLS的过程发育。
Oligodendrocytes (OLs) extend arborized processes that are supported by microtubules (MTs) and microfilaments. Little is known about proteins that modulate and interact with the cytoskeleton during myelination. Several lines of evidence suggest a role for 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) in mediating process formation in OLs. In this study, we report that tubulin is a major CNP-interacting protein. In vitro, CNP binds preferentially to tubulin heterodimers compared with MTs and induces MT assembly by copolymerizing with tubulin. CNP overexpression induces dramatic morphology changes in both glial and nonglial cells, resulting in MT and F-actin reorganization and formation of branched processes. These morphological effects are attributed to CNP MT assembly activity; branched process formation is either substantially reduced or abolished with the expression of loss-of-function mutants. Accordingly, cultured OLs from CNP-deficient mice extend smaller outgrowths with less arborized processes. We propose that CNP is an important component of the cytoskeletal machinery that directs process outgrowth in OLs.
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发表时间: 1992-04
期刊: The Journal of cell biology
影响因子: --
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