Clustering of integrin β cytoplasmic domains triggers nascent adhesion formation and reveals a protozoan origin of the integrin-talin interaction

被引:17
作者
Baade, Timo [1 ,2 ]
Paone, Christoph [1 ,2 ]
Baldrich, Adrian [1 ]
Hauck, Christof R. [1 ,2 ]
机构
[1] Univ Konstanz, Lehrstuhl Zellbiol, D-78457 Constance, Germany
[2] Univ Konstanz, Konstanz Res Sch Chem Biol, D-78457 Constance, Germany
关键词
VINCULIN BINDING; RECEPTOR; ACTIVATION; RECRUITMENT; MOLECULES; DYNAMICS; ADHESOME; PAXILLIN; CEACAM3; KINASE;
D O I
10.1038/s41598-019-42002-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Integrins and integrin-dependent cell-matrix adhesions are essential for a number of physiological processes. Integrin function is tightly regulated via binding of cytoplasmic proteins to integrin intracellular domains. Yet, the complexity of cell-matrix adhesions in mammals, with more than 150 core adhesome proteins, complicates the analysis of integrin-associated protein complexes. Interestingly, the evolutionary origin of integrins dates back before the transition from unicellular life to complex multicellular animals. Though unicellular relatives of metazoa have a less complex adhesome, nothing is known about the initial steps of integrin activation and adhesion complex assembly in protozoa. Therefore, we developed a minimal, microscope-based system using chimeric integrins to investigate receptor-proximal events during focal adhesion assembly. Clustering of the human integrin beta 1 tail led to recruitment of talin, kindlin, and paxillin and mutation of the known talin binding site abolished recruitment of this protein. Proteins indirectly linked to integrins, such as vinculin, migfilin, p130(CAS), or zyxin were not enriched around the integrin beta 1 tail. With the exception of integrin beta 4 and integrin beta 8, the cytoplasmic domains of all human integrin beta subunits supported talin binding. Likewise, the cytoplasmic domains of integrin beta subunits expressed by the protozoan Capsaspora owczarzaki readily recruited talin and this interaction was based on an evolutionary conserved NPXY/F amino acid motif. The results we present here validate the use of our novel microscopic assay to uncover details of integrin-based protein-protein interactions in a cellular context and suggest that talin binding to integrin beta cytoplasmic tails is an ancient feature of integrin regulation.
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页数:13
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