Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

Kindlin-1 通过与整合素和 Plk-1 相互作用来调节有丝分裂纺锤体的形成

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作者:Hitesh Patel, Judith Zich, Bryan Serrels, Colin Rickman, Kevin G Hardwick, Margaret C Frame, Valerie G Brunton

Abstract

Kindlin-1 binds to integrins and regulates integrin activation at cell adhesions. Here we report a new function of Kindlin-1 in regulating spindle assembly. We show that Kindlin-1 localizes to centrosomes, its concentration peaking during G2/M, where it associates with various pericentriolar material proteins, including Polo-like kinase 1. Short interfering RNA-mediated depletion of Kindlin-1 increases formation of abnormal mitotic spindles and decreases cellular survival. This effect is dependent not only on the ability of Kindlin-1 to bind integrins but also on Polo-like kinase 1-mediated Kindlin-1 phosphorylation. We demonstrate that a subcellular pool of phosphorylated Kindlin-1 is located exclusively at centrosomes. Our work identifies a novel cellular role for Kindlin-1 in ensuring mitotic spindle assembly and cellular survival that is controlled by phosphorylation via Polo-like kinase 1.

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