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在体功能分析揭示了整合素结合位点在 talin 中的特定作用。

In vivo functional analysis reveals specific roles for the integrin-binding sites of talin.

机构信息

Department of Cellular and Physiological Sciences, University of British Columbia, Life Science Institute, 2350 Health Sciences Mall, Vancouver, BC V6T1Z3, Canada.

出版信息

J Cell Sci. 2011 Jun 1;124(Pt 11):1844-56. doi: 10.1242/jcs.083337. Epub 2011 May 10.

DOI:10.1242/jcs.083337
PMID:21558413
Abstract

Adhesion receptors play diverse roles during animal development and require precise spatiotemporal regulation, which is achieved through the activity of their binding partners. Integrins, adhesion receptors that mediate cell attachment to the extracellular matrix (ECM), connect to the intracellular environment through the cytoplasmic adapter protein talin. Talin has two essential functions: orchestrating the assembly of the intracellular adhesion complex (IAC), which associates with integrin, and regulating the affinity of integrins for the ECM. Talin can bind to integrins through two different integrin-binding sites (IBS-1 and IBS-2, respectively). Here, we have investigated the roles of each in the context of Drosophila development. We find that although IBS-1 and IBS-2 are partially redundant, they each have specialized roles during development: IBS-1 reinforces integrin attachment to the ECM, whereas IBS-2 reinforces the link between integrins and the IAC. Disruption of each IBS has different developmental consequences, illustrating how the functional diversity of integrin-mediated adhesion is achieved.

摘要

黏附受体在动物发育过程中发挥多种作用,需要通过其结合伴侣的活性来实现精确的时空调节。整合素是介导细胞与细胞外基质(ECM)附着的黏附受体,通过细胞质衔接蛋白 talin 与细胞内环境相连。Talin 具有两个基本功能:协调与整合素相关的细胞内黏附复合物(IAC)的组装,以及调节整合素与 ECM 的亲和力。Talin 可以通过两个不同的整合素结合位点(分别为 IBS-1 和 IBS-2)与整合素结合。在这里,我们研究了每个结合位点在果蝇发育中的作用。我们发现,尽管 IBS-1 和 IBS-2 部分冗余,但它们在发育过程中各有专门的作用:IBS-1 增强整合素与 ECM 的附着,而 IBS-2 增强整合素与 IAC 之间的联系。每个 IBS 的破坏都有不同的发育后果,这说明了整合素介导的黏附的功能多样性是如何实现的。

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