Centre for Mechanochemical Cell Biology and Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK
Centre for Mechanochemical Cell Biology and Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
J Cell Biol. 2019 Nov 4;218(11):3548-3559. doi: 10.1083/jcb.201809089. Epub 2019 Oct 9.
Tropomyosin is a coiled-coil actin binding protein key to the stability of actin filaments. In muscle cells, tropomyosin is subject to calcium regulation, but its regulation in nonmuscle cells is not understood. Here, we provide evidence that the fission yeast tropomyosin, Cdc8, is regulated by phosphorylation of a serine residue. Failure of phosphorylation leads to an increased number and stability of actin cables and causes misplacement of the division site in certain genetic backgrounds. Phosphorylation of Cdc8 weakens its interaction with actin filaments. Furthermore, we show through in vitro reconstitution that phosphorylation-mediated release of Cdc8 from actin filaments facilitates access of the actin-severing protein Adf1 and subsequent filament disassembly. These studies establish that phosphorylation may be a key mode of regulation of nonmuscle tropomyosins, which in fission yeast controls actin filament stability and division site placement.
原肌球蛋白是一种卷曲螺旋肌动蛋白结合蛋白，对肌动蛋白丝的稳定性至关重要。在肌肉细胞中，原肌球蛋白受钙离子调节，但在非肌肉细胞中的调节机制尚不清楚。在这里，我们提供的证据表明，裂殖酵母原肌球蛋白 Cdc8 通过丝氨酸残基的磷酸化来调节。磷酸化失败会导致肌动蛋白电缆的数量和稳定性增加，并导致在某些遗传背景下分裂位点的错位。Cdc8 的磷酸化会削弱其与肌动蛋白丝的相互作用。此外，我们通过体外重组实验表明，磷酸化介导的 Cdc8 从肌动蛋白丝上的释放有助于肌动蛋白切割蛋白 Adf1 的进入，从而导致随后的纤维解体。这些研究表明，磷酸化可能是调节非肌肉原肌球蛋白的关键方式，在裂殖酵母中控制肌动蛋白丝的稳定性和分裂位点的定位。
