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力依赖性调节粘着斑处的 talin-KANK1 复合物。

Force-Dependent Regulation of Talin-KANK1 Complex at Focal Adhesions.

机构信息

Mechanobiology Institute , National University of Singapore , Singapore.

Department of Physics , National University of Singapore, Singapore.

出版信息

Nano Lett. 2019 Sep 11;19(9):5982-5990. doi: 10.1021/acs.nanolett.9b01732. Epub 2019 Aug 13.

Abstract

KANK proteins mediate cross-talk between dynamic microtubules and integrin-based adhesions to the extracellular matrix. KANKs interact with the integrin/actin-binding protein talin and with several components of microtubule-stabilizing cortical complexes. Because of actomyosin contractility, the talin-KANK complex is likely under mechanical force, and its mechanical stability is expected to be a critical determinant of KANK recruitment to focal adhesions. Here, we quantified the lifetime of the complex of the talin rod domain R7 and the KN domain of KANK1 under shear-force geometry and found that it can withstand forces for seconds to minutes over a physiological force range up to 10 pN. Complex stability measurements combined with cell biological experiments suggest that shear-force stretching promotes KANK1 localization to the periphery of focal adhesions. These results indicate that the talin-KANK1 complex is mechanically strong, enabling it to support the cross-talk between microtubule and actin cytoskeleton at focal adhesions.

摘要

KANK 蛋白介导动态微管和整合素基细胞外基质黏附之间的串扰。KANKs 与整合素/肌动蛋白结合蛋白 talin 以及微管稳定皮质复合物的几个成分相互作用。由于肌动球蛋白的收缩性,talin-KANK 复合物可能受到机械力的作用,其机械稳定性预计是 KANK 募集到焦点黏附的关键决定因素。在这里,我们在剪切力几何形状下定量测定了 talin 杆结构域 R7 和 KANK1 的 KN 结构域之间的复合物的寿命,并发现它可以在生理力范围内承受几秒钟到几分钟的力,力高达 10 pN。复合物稳定性测量与细胞生物学实验相结合表明,剪切力拉伸促进 KANK1 定位于焦点黏附的外围。这些结果表明,talin-KANK1 复合物具有很强的机械稳定性,使其能够在焦点黏附处支持微管和肌动蛋白细胞骨架之间的串扰。

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