Mesh : Actinin / metabolism Animals Cell Adhesion / drug effects Cell Line, Tumor Cells, Cultured Cluster Analysis Focal Adhesions / drug effects metabolism Humans Immunoblotting Integrins / metabolism K562 Cells Kinetics Mass Spectrometry Mice Microscopy, Fluorescence Nocodazole / pharmacology Paxillin / metabolism Protein Interaction Maps Proteome / classification metabolism Proteomics / methods Talin / metabolism Tubulin Modulators / pharmacology Vinculin / metabolism Zyxin / metabolism

来  源:   DOI:10.1038/ncb3257   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Integrin receptor activation initiates the formation of integrin adhesion complexes (IACs) at the cell membrane that transduce adhesion-dependent signals to control a multitude of cellular functions. Proteomic analyses of isolated IACs have revealed an unanticipated molecular complexity; however, a global view of the consensus composition and dynamics of IACs is lacking. Here, we have integrated several IAC proteomes and generated a 2,412-protein integrin adhesome. Analysis of this data set reveals the functional diversity of proteins in IACs and establishes a consensus adhesome of 60 proteins. The consensus adhesome is likely to represent a core cell adhesion machinery, centred around four axes comprising ILK-PINCH-kindlin, FAK-paxillin, talin-vinculin and α-actinin-zyxin-VASP, and includes underappreciated IAC components such as Rsu-1 and caldesmon. Proteomic quantification of IAC assembly and disassembly detailed the compositional dynamics of the core cell adhesion machinery. The definition of this consensus view of integrin adhesome components provides a resource for the research community.
摘要:
整联蛋白受体活化引发细胞膜上整联蛋白粘附复合物(IAC)的形成,其转导粘附依赖性信号以控制多种细胞功能。分离的IAC的蛋白质组学分析揭示了一个意想不到的分子复杂性;然而,缺乏对IAC的共识构成和动态的全球观点。这里,我们已经整合了几个IAC蛋白质组,并产生了2,412蛋白整合素粘附。对该数据集的分析揭示了IAC中蛋白质的功能多样性,并建立了60种蛋白质的共识。共识粘附可能代表核心细胞粘附机制,以四个轴为中心,包括ILK-PINCH-kindlin,FAK-桩蛋白,talin-vinoculin和α-actinin-zyxin-VASP,并包括未被重视的IAC组件,如Rsu-1和caldesmon。IAC组装和拆卸的蛋白质组学定量详细说明了核心细胞粘附机制的组成动力学。整合素粘附成分的这种共识观点的定义为研究界提供了资源。
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