Conserved Phosphorylation of the Myosin1e TH1 Domain Impacts Membrane Association and Function in Yeast and Worms

肌球蛋白1e TH1结构域的保守磷酸化影响酵母和线虫中的膜结合和功能

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Abstract

Cells have an intrinsic ability to rapidly respond to environmental change to regulate cell cycle progression and membrane organisation, thereby affecting cell growth and division. The actin cytoskeleton is a highly dynamic complex of proteins that can rapidly reorganise to change the growth pattern of a cell. Class I myosins are monomeric actin-associated motor proteins that play key roles in diverse cellular functions such as tension sensing and membrane reorganisation, as well as promoting actin polymer nucleation at sites of cell growth. We have analysed the localisation and function of both C. elegans class 1 myosins, HUM-1 (Myo1e) and HUM-5 (Myo1d). Both motors are non-essential. While HUM-1 is expressed in diverse cells and tissues, HUM-5 localises exclusively to a subset of cells in the nervous system. While animals lacking hum-1 displayed a reduced maximal brood size and a delay in embryo release, deleting both hum-1 and hum-5 together shortened C. elegans lifespan. Moreover, we identified that phosphorylation of a conserved serine residue within the Myo1e TH1 domain had an impact on the localisation and function of the motor protein in both C. elegans and the fission yeast, S. pombe, indicating this modification modulates the ability of Myo1e/HUM-1 to interact with phospholipids at the plasma membrane. We conclude that TH1 domain phosphorylation plays a key role in regulating the cellular distribution and function of Myo1e motors across all eukaryotes.

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