Beta1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination.
Beta1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination.
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DOI：
10.1083/jcb.200610014
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发表时间：
2007-06-18
影响因子：
7.8
通讯作者：
Feltri, M Laura
中科院分区：
文献类型：
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作者：
Nodari, Alessandro;Zambroni, Desiree;Quattrini, Angelo;Court, Felipe A;D'Urso, Alessandra;Recchia, Alessandra;Tybulewicz, Victor L J;Wrabetz, Lawrence;Feltri, M Laura
髓磷脂是围绕轴突的神经胶质膜的多螺旋延伸。神经胶质细胞是如何扩展到比它们的身体大很多倍的表面的，人们对此知之甚少。雪旺细胞是外周神经胶质细胞，并将放射状细胞质延伸插入轴突束中以对其进行分类、包鞘和髓鞘化。层粘连蛋白和β1整合素是轴突分选所必需的，但下游信号在很大程度上是未知的。我们发现缺乏β1整合素的雪旺细胞迁移到轴突上并在轴突上伸长，但不能延伸细胞质的放射状层，类似于具有低Rac 1活化的细胞。因此，在β1整合素缺失的神经中活性Rac 1减少，抑制Rac 1活性减少雪旺细胞中的放射状层，并且在转基因小鼠的雪旺细胞中消融Rac 1延迟轴突分选并损害髓鞘形成。最后，在β1整合素缺失的神经中表达活性Rac 1可改善分选。因此，β1整合素对Rac 1的激活增加，使许旺细胞从迁移/伸长转变为轴突分选和髓鞘形成所需的放射状膜的延伸。
Myelin is a multispiraled extension of glial membrane that surrounds axons. How glia extend a surface many-fold larger than their body is poorly understood. Schwann cells are peripheral glia and insert radial cytoplasmic extensions into bundles of axons to sort, ensheath, and myelinate them. Laminins and β1 integrins are required for axonal sorting, but the downstream signals are largely unknown. We show that Schwann cells devoid of β1 integrin migrate to and elongate on axons but cannot extend radial lamellae of cytoplasm, similar to cells with low Rac1 activation. Accordingly, active Rac1 is decreased in β1 integrin–null nerves, inhibiting Rac1 activity decreases radial lamellae in Schwann cells, and ablating Rac1 in Schwann cells of transgenic mice delays axonal sorting and impairs myelination. Finally, expressing active Rac1 in β1 integrin–null nerves improves sorting. Thus, increased activation of Rac1 by β1 integrins allows Schwann cells to switch from migration/elongation to the extension of radial membranes required for axonal sorting and myelination.