title: Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes.
abstract: A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3-aPKC complex to leave the cortex. Our findings illustrate how microtubules, independently of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC.
authors: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Center for Cell Dynamics, Johns Hopkins University School of Medicine, 725 N. Wolfe St., PCTB 706, Baltimore, Maryland 21205, USA.
authors: Fumio
authors: F
authors: Motegi
authors: Seth
authors: S
authors: Zonies
authors: Yingsong
authors: Y
authors: Hao
authors: Adrian A
authors: AA
authors: Cuenca
authors: Erik
authors: E
authors: Griffin
authors: Geraldine
authors: G
authors: Seydoux
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity; D008870:Microtubules / Q000201:enzymology* / Q000235:genetics; D009097:Multienzyme Complexes; D054731:PDZ Domains; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D015053:Zygote / Q000201:enzymology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D009097:Multienzyme Complexes; D011993:Recombinant Fusion Proteins; C087977:par-2 protein, C elegans; C409406:PAR-1 protein, C elegans; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C