WNK1 is involved in Nogo66 inhibition of OPC differentiation
WNK1 is involved in Nogo66 inhibition of OPC differentiation
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WNK1 参与 Nogo66 对 OPC 分化的抑制。
DOI：
10.1016/j.mcn.2015.03.003
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发表时间：
2015-03-01
影响因子：
3.5
通讯作者：
Xu, Xiao-Hui
中科院分区：
文献类型：
--
作者：
Zhang, Zhao-Huan;Li, Jiao-Jiao;Xu, Xiao-Hui
LINGO-1是主要在中枢神经系统（CNS）中表达的跨膜受体，并且在髓鞘形成中起重要作用。最近的研究表明，它也参与了少突胶质细胞前体细胞（OPC）的生存和分化;然而，OPC发展的下游信号通路是未知的。在我们之前的研究中，我们发现LINGO-1与WNK 1在通过RhoA激活介导Nogo诱导的神经突起延伸抑制中相关。为了鉴定LINGO-1-WNK 1在OPCs中的作用，我们首先证实了WNK 1也在OPCs中表达，并与LINGO-1共定位，LINGO-1通过RNA干扰减弱Nogo 66诱导的OPC分化抑制来抑制WNK 1的表达。此外，我们使用几个片段化的肽绘制了WNK 1激酶结构域，以确定与LINGO-1相互作用的关键区域。我们发现，对应于D 6肽的序列是相互作用所必需的。最后，我们发现使用TAT-D 6肽将D 6肽引入原代培养的OPC中抑制LINGO-1和WNK 1之间的缔合，并显著减弱Nogo 66诱导的OPC分化抑制。总之，我们的结果表明，WNK 1，通过WNK 1激酶结构域上的特定区域，与LINGO-1相互作用，从而介导Nogo 66抑制的OPC分化。(C)2015 Elsevier Inc. All rights reserved.
LINGO-1 is a transmembrane receptor expressed primarily in the central nervous system (CNS) and plays an important role in myelination. Recent studies have indicated that it is also involved in oligodendrocyte precursor cell (OPC) survival and differentiation; however, the downstream signaling pathway underlying OPC development is unknown. In our previous study, we found that LINGO-1 is associated with WNK1 in mediating Nogo-induced neurite extension inhibition by RhoA activation. In an effort to identify the role of LINGO-1-WNK1 in OPCs, we first confirmed that WNK1 is also expressed in OPCs and co-localized with LINGO-I, which suppresses WNK1 expression by RNA interference-attenuated Nogo66-induced inhibition of OPC differentiation. Furthermore, we mapped the WNK1 kinase domain using several fragmented peptides to identify the key region of interaction with LINGO-1. We found that a sequence corresponding to the D6 peptide is necessary for the interaction. Finally, we found that using the TAT-D6 peptide to introduce D6 peptide into primary cultured OPC inhibits the association between LINGO-1 and WNK1 and significantly attenuates Nogo66-induced inhibition of OPC differentiation. Taken together, our results show that WNK1, via a specific region on WNK1 kinase domain, interacts with LINGO-1, thus mediating Nogo66-inhibited OPC differentiation. (C) 2015 Elsevier Inc. All rights reserved.