MARK2 regulates directed cell migration through modulation of myosin II contractility and focal adhesion organization

• DOI: 10.1016/j.cub.2022.04.088
• Publication Date: 2022-05-19T14:29:13Z
• Authors: Ana M. Pasapera; Sarah M. Heissler; Masumi Eto; Yukako Nishimura; Robert S. Fischer; Hawa R. Thiam; Clare M. Waterman
• Keywords: Contractility

Cancer cell migration during metastasis is mediated by a highly polarized cytoskeleton. MARK2 and its invertebrate homolog Par1B are kinases that regulate the microtubule cytoskeleton to mediate polarization of neurons in mammals embryos invertebrates. However, role cancer unclear. Using osteosarcoma cells, we found addition known localizations on microtubules plasma membrane, also associates with actomyosin focal adhesions. Cells depleted MARK proteins demonstrated promotes phosphorylation both myosin II phosphatase targeting subunit MYPT1 synergistically drive contractility stress fiber formation cells. Studies isolated showed directly phosphorylates regulatory light chain, while effects indirect. mutant lacking membrane-binding domain, membrane association required for adhesion MARK2, where it specifically enhances protrusion promoting FAK adhesions oriented direction directionally persistent motility. Together, our results define as master regulator cytoskeletal systems directional migration.