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, T(186), essential for polo binding and show that T(186) is important for MEX-5 function in vivo. We also show that MBK-2, a developmentally regulated DYRK2 kinase activated at meiosis II, primes T(186) for subsequent polo kinase-dependent phosphorylation. Prior phosphorylation of MEX-5 at T(186) 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.
Nishi
Yuichi
Y
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Rogers
Eric
E
Robertson
Scott M
SM
Lin
Rueyling
R
D000818:Animals; D019521:Body Patterning; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D016764:Cell Polarity; D003593:Cytoplasm / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000201:enzymology*; D005455:Fluorescent Antibody Technique; D017238:Genes, Helminth; D017930:Genes, Reporter; D005854:Germ Cells; D049452:Green Fluorescent Proteins / Q000378:metabolism; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000097603:Dyrk Kinases; D000097869:Polo-Like Kinase 1
D029742:Caenorhabditis elegans Proteins; D049452:Green Fluorescent Proteins; D010769:Phosphothreonine; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases; C410587:MEX-5 protein, C elegans; C410589:MEX-6 protein, C elegans; C513017:plk-1 protein, C elegans; D000097869:Polo-Like Kinase 1