A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex1,2. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance1,2, 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.
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This study was supported by the Japan Society for the Promotion of Science (F.M.), the American Cancer Society (PF-08-158-01; E.G.) and the National Institute of Health (R01HD37047; G.S.). G.S. is an investigator of the Howard Hughes Medical Institute. We thank J. Ahringer, A. Audhya, L. Boyd, A. Desai, P. Gonczy, M. Gotta, R. Green, C. Hoege, K. Kemphues, Y. Nishimura, K. F. O’Connell, K. Oegema, L. S. Rose, A. Sugimoto, C. M. Waterman, H. Zaher and the Caenorhabditis Genetic Center for reagents and expertise.
The authors declare no competing financial interests.
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Motegi, F., Zonies, S., Hao, Y. et al. Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes. Nat Cell Biol 13, 1361–1367 (2011). https://doi.org/10.1038/ncb2354
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