Phosphodieterase-Iα/autotaxin and IFAK phosphorylation during controls cytoskeletal organization myelination
Phosphodieterase-Iα/autotaxin and IFAK phosphorylation during controls cytoskeletal organization myelination
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DOI：
10.1016/j.mcn.2004.06.002
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发表时间：
2004-10-01
影响因子：
3.5
通讯作者：
Fuss, B
中科院分区：
文献类型：
--
作者：
Fox, MA;Alexander, JK;Fuss, B
中枢神经系统（CNS）内的髓鞘形成涉及少突胶质细胞的大量形态发生，需要少突胶质细胞-细胞外基质（ECM）相互作用（即粘附）的可塑性变化。我们以前的研究表明，这种粘附可塑性的调节剂是少突胶质细胞释放的磷酸二酯酶-I α/自分泌运动因子（PD-I α/ATX）。我们在这里报告，PD-Ialpha/ATX的粘附拮抗作用是由一种不同于刺激肿瘤细胞运动的蛋白质片段介导的。此外，PD-I α/ATX的粘附拮抗片段导致粘着斑组分粘着斑蛋白和桩蛋白的重组分布以及粘着斑激酶（FAK）酪氨酸残基925（pFAK-925）磷酸化的整合素依赖性降低。在体内，当PD-1 α/ATX表达显著上调时，在髓鞘形成开始时发生类似的pFAK-925减少。最重要的是，它也可以通过应用外源性PD-I α/ATX诱导。因此，我们的数据表明，PD-I α/ATX通过一种新的信号通路参与髓鞘形成的调节，导致整合素依赖性粘着斑组装的变化，从而导致少突胶质细胞-ECM相互作用。(C)2004爱思唯尔公司All rights reserved.
Myelination within the central nervous system (CNS) involves substantial morphogenesis of oligodendrocytes requiring plastic changes in oligodendrocyte-extracellular matrix (ECM) interactions, that is, adhesion. Our previous studies indicated that a regulator of such adhesive plasticity is oligodendrocyte-released phosphodiesterase-Ialpha/autotaxin (PD-Ialpha/ATX). We report here, that PD-Ialpha/ATX's adhesion antagonism is mediated by a protein fragment different from the one that stimulates tumor cell motility. Furthermore, PD-Ialpha/ATX's adhesion-antagonizing fragment causes a reorganized distribution of the focal adhesion components vinculin and paxillin and an integrin-dependent reduction in focal adhesion kinase (FAK) phosphorylation at tyrosine residue 925 (pFAK-925). In vivo, a similar reduction in pFAK-925 occurs at the onset of myelination when PD-Ialpha/ATX expression is significantly upregulated. Most importantly, it can also be induced by the application of exogenous PD-Ialpha/ATX. Our data, therefore, suggest that PD-Ialpha/ATX participates in the regulation of myelination via a novel signaling pathway leading to changes in integrin-dependent focal adhesion assembly and consequently oligodendrocyte-ECM interactions. (C) 2004 Elsevier Inc. All rights reserved.