Hao Yingsong, Boyd Lynn, Seydoux Geraldine
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dev Cell. 2006 Feb;10(2):199-208. doi: 10.1016/j.devcel.2005.12.015.
Asymmetric localization of PAR proteins is a hallmark of polarized cells, but the mechanisms that create PAR asymmetry are not well understood. In the C. elegans zygote, PAR asymmetry is initiated by a transient actomyosin contraction, which sweeps the PAR-3/PAR-6/PKC-3 complex toward the anterior pole of the egg. The RING finger protein PAR-2 accumulates in a complementary pattern in the posterior cortex. Here we present evidence that PAR-2 participates in a feedback loop to stabilize polarity. PAR-2 is a target of the PKC-3 kinase and is excluded from the anterior cortex by PKC-3-dependent phosphorylation. The RING domain of PAR-2 is required to overcome inhibition by PKC-3 and stabilize PAR-2 on the posterior cortex. Cortical PAR-2 in turn prevents PAR-3/PAR-6/PKC-3 from returning to the posterior, in a PAR-1- and PAR-5-dependent manner. Our findings suggest that reciprocal inhibitory interactions among PAR proteins stabilize polarity by reinforcing an initial asymmetry in PKC-3.
PAR蛋白的不对称定位是极化细胞的一个标志，但产生PAR不对称的机制尚未完全了解。在秀丽隐杆线虫受精卵中，PAR不对称由短暂的肌动球蛋白收缩引发，该收缩将PAR-3/PAR-6/PKC-3复合物扫向卵的前极。泛素连接酶蛋白PAR-2在后皮质以互补模式积累。在此，我们提供证据表明PAR-2参与一个反馈环以稳定极性。PAR-2是PKC-3激酶的一个靶点，并通过PKC-3依赖的磷酸化作用被排除在前皮质之外。PAR-2的泛素连接酶结构域是克服PKC-3抑制并在后皮质稳定PAR-2所必需的。皮质PAR-2继而以PAR-1和PAR-5依赖的方式阻止PAR-3/PAR-6/PKC-3回到后部。我们的研究结果表明，PAR蛋白之间的相互抑制性相互作用通过加强PKC-3中的初始不对称来稳定极性。
