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.
Nat Cell Biol. 2011 Oct 9;13(11):1361-7. doi: 10.1038/ncb2354.
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.
极化细胞的一个标志是 PAR 极性调节因子在细胞皮层中分离成不对称的域。涉及两种保守激酶、非典型蛋白激酶 C（aPKC）和 PAR-1 的拮抗相互作用已被牵涉到维持极性，但启动不对称 PAR 域形成的机制尚不清楚。在这里，我们描述了精子捐献的中心体在秀丽隐杆线虫合子中用于极化 PAR 蛋白的一种途径。在极化之前，皮质 aPKC 通过磷酸化排除 PAR-1 激酶及其结合伙伴 PAR-2。在对称性破坏期间，由中心体引发的微管局部保护 PAR-2 免受 aPKC 的磷酸化，从而使 PAR-2 和 PAR-1 能够进入最接近中心体的皮质。皮质 PAR-1 磷酸化 PAR-3，导致 PAR-3-aPKC 复合物离开皮质。我们的发现说明了微管如何通过提供局部保护来防止 aPKC 施加的全局障碍，从而独立于肌动蛋白动力学来刺激 PAR 蛋白的自我组织。
