Dual specificity kinase DYRK3 regulates cell migration by influencing the stability of protrusions
Description
Plasma membrane-associated platforms (PMAPs) form at specific sites of plasma membrane by scaffolds including ERC1 and Liprin-1. We identify a mechanism regulating PMAPs assembly, with consequences on motility/invasion. Silencing Ser/Thr kinase DYRK3 in invasive breast cancer cells inhibits their motility and invasive capacity. Similar effects on motility were observed by increasing DYRK3 levels, while kinase-dead DYRK3 had limited effects. DYRK3 overexpression inhibits PMAPs formation nad has negative effects on stability of lamellipodia and adhesions in migrating cells. Liprin-1 depletion results in unstable lamellipodia and impaired cell motility. DYRK3 causes increased Liprin-1 phosphorylation. Increasing levels of Liprin-1 rescue the inhibitory effects of DYRK3 on cell spreading, suggesting that an equilibrium between Liprin-1 and DYRK3 levels is required for lamellipodia stability and tumor cell motility. Our results show that DYRK3 is relevant to tumor cell motility, and identify a PMAP target of the kinase, highlighting a new mechanism regulating cell edge dynamics. Upon request, the corresponding author is available to provide the data in different formats if it is not possible to open data files with open-source softwares.