Schwannomin/merlin promotes Schwann cell elongation and influences myelin segment length.

Schwannomin/merlin promotes Schwann cell elongation and influences myelin segment length.
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DOI:
10.1016/j.mcn.2010.12.006
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发表时间:
2011-05
影响因子:
3.5
通讯作者:
Fernandez-Valle, Cristina
Fernandez-Valle, Cristina
中科院分区:
医学3区
文献类型:
--
作者:
Thaxton, Courtney;Bott, Marga;Walker, Barbara;Sparrow, Nicklaus A.;Lambert, Stephen;Fernandez-Valle, Cristina

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神经纤维瘤病2型肿瘤抑制因子,神经鞘蛋白(schwannomin,Sch)是一种调节受体信号和肌动蛋白动力学的质膜-细胞骨架连接蛋白。我们研究了雪的作用,在指定的形态学变化所需的雪旺细胞(SC)的功能在体外。分离的Sch-GFP表达的SC延长双极过程比GFP表达细胞形成的过程长82%。相比之下,表达显性阴性Sch-BBA-GFP的SC延长双极过程比对照短16%,比表达Sch-GFP的SC短64%。nf 2基因失活导致分离的小鼠SC从双极细胞向多极细胞转变。实时成像显示,SC共表达Sch-GFP和显性阴性RacN 17表现出类似的背根神经节外植体培养物,他们迅速对齐轴突和缓慢延长双极过程。相反,表达组成型活性RacV 12的SC在形态上经历了连续的转变,这干扰了轴突排列。当与神经元在髓鞘促进条件下共培养时,Sch-GFP表达的SC比GFP表达的SC产生更长的髓鞘段。相比之下,表达Sch-BBA-GFP的SC未能在轴突上对齐或形成髓鞘。总之,这些结果表明,Sch在诱导和/或维持SC的纺锤体形状中起着至关重要的作用,并表明该机制涉及Sch依赖性抑制Rac活性。通过稳定双极形态,Sch促进SC与轴突对齐,并最终影响髓鞘段长度。
The Neurofibromatosis type 2 tumor suppressor, schwannomin (Sch) is a plasma membrane-cytoskeleton linking protein that regulates receptor signaling and actin dynamics. We examined Sch’s role in specifying morphological changes needed for Schwann cell (SC) function in vitro. Isolated Sch-GFP-expressing SCs extended bipolar processes 82% longer than those formed by GFP-expressing cells. In contrast, SCs expressing dominant negative Sch-BBA-GFP extended bipolar processes 16% shorter than controls and 64% shorter than Sch-GFP-expressing SCs. nf2 gene inactivation caused isolated mouse SCs to transition from bipolar to multipolar cells. Live imaging revealed that SCs co-expressing Sch-GFP and dominant negative RacN17 behaved similarly in dorsal root ganglion explant cultures; they quickly aligned on axons and slowly elongated bipolar processes. In contrast, SCs expressing constitutively active RacV12 underwent continuous transitions in morphology that interfered with axon alignment. When co-cultured with neurons under myelin-promoting conditions, Sch-GFP-expressing SCs elaborated longer myelin segments than GFP-expressing SCs. In contrast, Sch-BBA-GFP-expressing SCs failed to align on or myelinate axons. Together, these results demonstrate that Sch plays an essential role in inducing and/or maintaining the SC’s spindle shape and suggest that the mechanism involves Sch-dependent inhibition of Rac activity. By stabilizing the bipolar morphology, Sch promotes alignment of SCs with axons and ultimately influences myelin segment length.
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