LINGO-1-mediated inhibition of oligodendrocyte differentiation does not require the leucine-rich repeats and is reversed by p75NTR antagonists
LINGO-1-mediated inhibition of oligodendrocyte differentiation does not require the leucine-rich repeats and is reversed by p75NTR antagonists
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DOI：
10.1016/j.mcn.2010.07.009
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发表时间：
2010-12-01
影响因子：
3.5
通讯作者：
Walmsley, Adrian Robert
中科院分区：
文献类型：
--
作者：
Bourikas, Dimitris;Mir, Anis;Walmsley, Adrian Robert
LINGO 1是少突胶质细胞分化的有效负调节因子，因此可能在脱髓鞘疾病如多发性硬化的髓鞘再生过程中发挥关键的限制作用。然而，LINGO 1抑制少突胶质细胞分化的哪个阶段，涉及蛋白质的哪些结构域以及是否需要辅助蛋白，目前知之甚少。人少突胶质细胞系MO 3 13中LINGO-1的表达抑制了突起延伸，并且这被抗LINGO-1抗体或拮抗剂LINGO 1- 1逆转。还发现Fc LINGO 1表达抑制大鼠少突胶质细胞系CG 4中髓鞘碱性蛋白的转录。LINGO-1的功能通过缺失整个胞外域或胞质结构域而被消除，但令人惊讶的是不受富含亮氨酸的重复序列（LRR）缺失的影响。在神经元中，LINGO-1与MO 3 - 13细胞中的内源性p75（NTR）物理相关，相应地，其对过程延伸的抑制被p75（NTR）的拮抗剂逆转。1通过需要p75（NTR）信号传导的过程独立于LRR抑制少突胶质细胞分化的多个方面（C）2010 Elsevier Inc版权所有
LINGO 1 is a potent negative regulator of oligodendrocyte differentiation and hence may play a pivotal restrictive role during remyelination in demyelinating diseases such as multiple sclerosis However little is known as to which stages of oligodendrocyte differentiation are inhibited by LINGO 1 which domains of the protein are Involved and whether accessory proteins are required Here we show that LINGO-1 expression in the human oligodendroglial cell line MO3 13 inhibited process extension and this was reversed by an anti LINGO-1 antibody or the antagonist LINGO 1-Fc LINGO 1 expression was also found to inhibit myelin basic protein transcription in the rat oligodendroglial cell line CG4 Both of these inhibitory actions of LINGO 1 were abrogated by deletion of the entire ectodomain or cytoplasmic domains but surprisingly were unaffected by deletion of the leucine rich repeats (LRRs) As in neurons LINGO-1 physically associated with endogenous p75(NTR) in MO3 13 cells and correspondingly its inhibition of process extension was reversed by antagonists of p75(NTR) Thus LINGO-1 inhibits multiple aspects of oligodendrocyte differentiation independently of the LRRs via a process that requires p75(NTR) signalling (C) 2010 Elsevier Inc All rights reserved