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2007-8-27 17:32:00

8月23-24日Science & Nature内容精选

8月23日Nature

封面故事: 细胞间隙连接处探秘

间隙连接处是相邻细胞形成小孔或通道、让信号分子和离子在细胞之间自由通过的地方,它们存在于脊椎动物的很多成年细胞和正在发育的细胞中。它们的功能一直被认为在很大程度上是由于细胞之间的分子流动。但事情并不是这么简单。现在,Elias等人提供的证据表明,间隙连接处在神经迁移中发挥一定作用,而对迁移来说重要的是间隙连接蛋白的黏附性能及细胞之间接触点的性质,不是它们通道的导通性能。这一发现的意义已经超出了脑发育。因为很多其他间隙连接功能(包括参与肿瘤的转移)也可能取决于黏附性能而不是小孔功能,所以间隙连接处可能因以前没有被考虑到的方式而易于操控。本期封面所示为沿着脑中的放射状纤维爬行的神经元,而提供黏附接触的一团团间隙连接处用橙色显示。

英文原文:

Nature 448, 901-907 (23 August 2007) | doi:10.1038/nature06063; Received 9 April 2007; Accepted 6 July 2007

Gap junction adhesion is necessary for radial migration in the neocortex

Laura A. B. Elias1,2, Doris D. Wang1,2 & Arnold R. Kriegstein2

  1. Neuroscience Graduate Program,
  2. Institute for Regeneration Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143, USA

Correspondence to: Laura A. B. Elias1,2Arnold R. Kriegstein2 Correspondence and requests for materials should be addressed to L.A.B.E. (Email: EliasL@stemcell.ucsf.edu) or A.R.K. (Email: KriegsteinA@stemcell.ucsf.edu).

Abstract

Radial glia, the neuronal stem cells of the embryonic cerebral cortex, reside deep within the developing brain and extend radial fibres to the pial surface, along which embryonic neurons migrate to reach the cortical plate. Here we show that the gap junction subunits connexin 26 (Cx26) and connexin 43 (Cx43) are expressed at the contact points between radial fibres and migrating neurons, and acute downregulation of Cx26 or Cx43 impairs the migration of neurons to the cortical plate. Unexpectedly, gap junctions do not mediate neuronal migration by acting in the classical manner to provide an aqueous channel for cell–cell communication. Instead, gap junctions provide dynamic adhesive contacts that interact with the internal cytoskeleton to enable leading process stabilization along radial fibres as well as the subsequent translocation of the nucleus. These results indicate that gap junction adhesions are necessary for glial-guided neuronal migration, raising the possibility that the adhesive properties of gap junctions may have an important role in other physiological processes and diseases associated with gap junction function.

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