Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
J Cell Biol. 2010 Sep 6;190(5):793-805. doi: 10.1083/jcb.201002055. Epub 2010 Aug 30.
The mechanisms that regulate cytoskeletal remodeling during the transition between mitosis and interphase are poorly understood. In fission yeast the MOR pathway promotes actin polarization to cell tips in interphase, whereas the SIN signaling pathway drives actomyosin ring assembly and cytokinesis. We show that the SIN inhibits MOR signaling in mitosis by interfering with Nak1 kinase-mediated activation of the most downstream MOR component, the NDR family kinase Orb6. Inactivation of the MOR may be a key function of the SIN because attenuation of MOR signaling rescued the cytokinetic defects of SIN mutants and allowed weak SIN signaling to trigger ectopic cytokinesis. Furthermore, failure to inhibit the MOR is toxic when the cell division apparatus is compromised. Together, our results reveal a mutually antagonistic relationship between the SIN and MOR pathways, which is important for completion of cytokinesis and coordination of cytoskeletal remodeling at the mitosis-to-interphase transition.
尚不清楚有哪些机制调节有丝分裂向间期转换过程中的细胞骨架重塑。在裂殖酵母中，MOR 途径促进有丝分裂向间期的细胞尖端极化，而 SIN 信号通路则驱动肌动球蛋白环的组装和胞质分裂。我们发现，SIN 通过干扰 Nak1 激酶对最下游 MOR 成分 NDR 家族激酶 Orb6 的介导激活，在有丝分裂中抑制 MOR 信号。MOR 的失活可能是 SIN 的一个关键功能，因为减弱 MOR 信号可以挽救 SIN 突变体的胞质分裂缺陷，并使微弱的 SIN 信号触发异位胞质分裂。此外，当细胞分裂装置受损时，无法抑制 MOR 是有毒的。总之，我们的研究结果揭示了 SIN 和 MOR 途径之间的相互拮抗关系，这对于完成胞质分裂和协调有丝分裂向间期转换过程中的细胞骨架重塑非常重要。
