An interaction between myosin-10 and the cell cycle regulator Wee1 links spindle dynamics to mitotic progression in epithelia

肌球蛋白-10 与细胞周期调节剂 Wee1 之间的相互作用将纺锤体动力学与上皮细胞有丝分裂进程联系起来

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作者:Joshua C Sandquist, Matthew E Larson, Sarah Woolner, Zhiwei Ding, William M Bement

Abstract

Anaphase in epithelia typically does not ensue until after spindles have achieved a characteristic position and orientation, but how or even if cells link spindle position to anaphase onset is unknown. Here, we show that myosin-10 (Myo10), a motor protein involved in epithelial spindle dynamics, binds to Wee1, a conserved regulator of cyclin-dependent kinase 1 (Cdk1). Wee1 inhibition accelerates progression through metaphase and disrupts normal spindle dynamics, whereas perturbing Myo10 function delays anaphase onset in a Wee1-dependent manner. Moreover, Myo10 perturbation increases Wee1-mediated inhibitory phosphorylation on Cdk1, which, unexpectedly, concentrates at cell-cell junctions. Based on these and other results, we propose a model in which the Myo10-Wee1 interaction coordinates attainment of spindle position and orientation with anaphase onset.

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