The septin cytoskeleton in myelinating glia

The septin cytoskeleton in myelinating glia
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DOI:
10.1016/j.mcn.2008.10.002
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发表时间:
2009-02-01
影响因子:
3.5
通讯作者:
Schaeren-Wiemers, N.
Schaeren-Wiemers, N.
中科院分区:
医学3区
文献类型:
--
作者:
Buser, A. M.;Erne, B.;Schaeren-Wiemers, N.

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髓鞘被组织成具有不同蛋白质和脂质组成的亚结构域。目前尚不清楚这些域是如何建立和维护的。细胞骨架元件与膜组分相互作用可以产生和维持这样的结构域。在这里,我们证明了跨膜髓鞘蛋白MAL与细胞骨架蛋白隔蛋白6相互作用。隔膜蛋白代表了第四种参与膜区室化、囊泡运输和支架形成的丝状系统。我们报告说,多个septin复合物与髓鞘,它们显示重叠,但在中枢和外周神经系统的组成不相同。在周围神经和少突胶质细胞髓鞘形成过程中,septins不同亚群的表达上调。在PNS中,septins高度富集在非致密的髓鞘室中,特别是在结旁环和郎维尔结处的微绒毛中。重要的是,在髓鞘缺乏Septin 6的情况下,其最接近的同系物Sept11的丰度增加,表明功能性代偿作用。我们的数据表明,隔蛋白细胞骨架是髓鞘的一个组成部分,并与不同的髓鞘成分,如MAL.We的相互作用表明,隔蛋白是有趣的候选人在髓鞘节间膜区室化。(C)2008年爱思唯尔公司All rights reserved.
Myelin is organized in subdomains with distinct protein and lipid composition. How these domains are established and maintained is currently unknown. Cytoskeletal elements interacting with membrane components could generate and sustain such structural domains. Here, we demonstrate that the transmembrane myelin protein MAL interacts with the cytoskeleton protein septin 6. Septins represent a fourth filamentous system involved in membrane compartmentalization, vesicle transport and scaffold formation. We report that multiple septin complexes are associated with myelin, and that they display an overlapping but non-identical composition in the central and peripheral nervous system. The expression of distinct Subsets of septins was upregulated during myelin formation in peripheral nerves and oligodendrocytes. In the PNS, septins were highly enriched in non-compact myelin compartments, particularly in the paranodal loops and the microvilli at the node of Ranvier. Importantly in myelin lacking Septin 6, the abundance of its closest homolog Sept11 was increased, suggesting a functional compensatory role. Our data demonstrate that the septin cytoskeleton is an integral component of the myelin sheath and interacts with distinct myelin constituents such as MAL. We suggest that septins are intriguing candidates for membrane compartmentalization in myelin internodes. (C) 2008 Elsevier Inc. All rights reserved.