Polo kinases regulate C. elegans embryonic polarity via binding to DYRK2-primed MEX-5 and MEX-6

Polo kinases are known key regulators of cell divisions. Here we report a novel, non-cell division function for polo kinases in embryonic polarity of newly fertilized Caenorhabditis elegans embryos. We show that polo kinases, via their polo box domains, bind to and regulate the activity of two key polarity proteins, MEX-5 and MEX-6. These polo kinases are asymmetrically localized along the anteroposterior axis of newly fertilized C. elegans embryos in a pattern identical to that of MEX-5 and MEX-6. This asymmetric localization of polo kinases depends on MEX-5 and MEX-6, as well as genes regulating MEX-5 and MEX-6 asymmetry. We identify an amino acid of MEX-5, T₁₈₆, essential for polo binding and show that T₁₈₆ is important for MEX-5 function in vivo. We also show that MBK-2, a developmentally regulated DYRK2 kinase activated at meiosis II, primes T₁₈₆ for subsequent polo kinase-dependent phosphorylation. Prior phosphorylation of MEX-5 at T₁₈₆ greatly enhances phosphorylation of MEX-5 by polo kinases in vitro. Our results provide a mechanism by which MEX-5 and MEX-6 function is temporally regulated during the crucial oocyte-to-embryo transition.