Coordinate control of axon defasciculation and myelination by laminin-2 and -8.

Coordinate control of axon defasciculation and myelination by laminin-2 and -8.
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DOI:
10.1083/jcb.200411158
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发表时间:
2005-02-14
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Patton BL
Patton BL
中科院分区:
其他
文献类型:
--
作者:
Yang D;Bierman J;Tarumi YS;Zhong YP;Rangwala R;Proctor TM;Miyagoe-Suzuki Y;Takeda S;Miner JH;Sherman LS;Gold BG;Patton BL

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雪旺细胞形成含有层粘连蛋白-2(Ln-2;异源三聚体α2β1γ1)和Ln-8(α4β1γ1)的基底层(BL)。在携带α2链突变的人类和小鼠中,Ln-2的缺失会阻止发育中的许旺细胞完全去纤维化轴突,导致部分无髓鞘形成。主要的致病机制被认为是来源于Ln-2支架的雪旺细胞BL中的结构缺陷。然而,我们发现Ln-8的缺失导致小鼠部分无髓鞘化,而不影响BL结构或Ln-2水平。Ln-2/Ln-8联合缺乏导致几乎完全的无髓鞘形成,揭示Ln-2和Ln-8一起在去束形成中具有主导作用,并且Ln-8促进髓鞘形成而没有BL。转基因Ln-10(α5β1γ1)表达也促进髓鞘形成,但不形成BL。而不是BL结构,我们发现Ln-2和-8是特别需要的增加围产期施万细胞增殖,参加髓鞘形成。纯化的Ln-2和Ln-8与自分泌因子合作直接增强体外雪旺细胞增殖,表明Ln通过调节体内对有丝分裂原的反应来控制髓鞘形成的开始。
Schwann cells form basal laminae (BLs) containing laminin-2 (Ln-2; heterotrimer α2β1γ1) and Ln-8 (α4β1γ1). Loss of Ln-2 in humans and mice carrying α2-chain mutations prevents developing Schwann cells from fully defasciculating axons, resulting in partial amyelination. The principal pathogenic mechanism is thought to derive from structural defects in Schwann cell BLs, which Ln-2 scaffolds. However, we found loss of Ln-8 caused partial amyelination in mice without affecting BL structure or Ln-2 levels. Combined Ln-2/Ln-8 deficiency caused nearly complete amyelination, revealing Ln-2 and -8 together have a dominant role in defasciculation, and that Ln-8 promotes myelination without BLs. Transgenic Ln-10 (α5β1γ1) expression also promoted myelination without BL formation. Rather than BL structure, we found Ln-2 and -8 were specifically required for the increased perinatal Schwann cell proliferation that attends myelination. Purified Ln-2 and -8 directly enhanced in vitro Schwann cell proliferation in collaboration with autocrine factors, suggesting Lns control the onset of myelination by modulating responses to mitogens in vivo.
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