βIV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment

βIV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment
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DOI:
10.1016/j.mcn.2006.11.017
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发表时间:
2007-03-01
影响因子:
3.5
通讯作者:
Kamiguchi, Hiroyuki
Kamiguchi, Hiroyuki
中科院分区:
医学3区
文献类型:
--
作者:
Nishimura, Kazunari;Akiyama, Hiroki;Kamiguchi, Hiroyuki

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极化神经元的轴突和体树突质膜表达不同的功能分子。已知神经元极性可通过阻碍两个域之间的膜组分的扩散混合的屏障来维持。使用PIV-血影蛋白基因敲除小鼠,我们证明了这种细胞骨架蛋白参与形成一个屏障,选择性地阻止L1细胞粘附分子(LICAM)在海马神经元轴突起始段的侧向移动。我们还表明,β IV-血影蛋白为基础的屏障是必需的轴突特异性分布的L1 ACAM在体外和体内。对L1 ACAM的屏障活性可能取决于L1 CAM与锚蛋白(G)(一种与PIV-血影蛋白结合的蛋白质)的直接相互作用,而不是取决于聚集在轴突起始段的其他跨膜蛋白的空间位阻。我们的研究结果强调了PIV-血影蛋白和锚蛋白(G)作为针对L1 CAM的选择性屏障的关键组分的作用。(c)2006年爱思唯尔公司All rights reserved.
Axonal and somatodendritic plasma membranes of polarized neurons express distinct sets of functional molecules. It is known that the neuronal polarity can be maintained by a barrier that impedes diffusional mixing of membrane components between the two domains. Using PIV-spectrin knockout mice, we demonstrate the involvement of this cytoskeletal protein in the formation of a barrier that selectively blocks lateral mobility of L1 cell adhesion molecule (LICAM) at the axon initial segment of hippocampal neurons. We also show that the beta IV-spectrin-based barrier is required for the axon-specific distribution of L1ACAM both in vitro and in vivo. The barrier activity against L1ACAM may depend on direct interactions of L1CAM with ankyrin(G), a protein binding to PIV-spectrin, rather than on steric hindrance by other transmembrane proteins clustered at the axon initial segment. Our results highlight the role of PIV-spectrin and ankyrin(G) as critical components of a selective barrier against L1CAM. (c) 2006 Elsevier Inc. All rights reserved.