Gupta Sneha, Govindaraghavan Meera, McCollum Dannel
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
Eukaryot Cell. 2014 Aug;13(8):1104-12. doi: 10.1128/EC.00129-14. Epub 2014 Jun 27.
NDR (nuclear Dbf-2-related) kinases constitute key regulatory nodes in signaling networks that control multiple biological processes such as growth, proliferation, mitotic exit, morphogenesis, and apoptosis. Two NDR pathways called the septation initiation network (SIN) and the morphogenesis Orb6 network (MOR) exist in the fission yeast Schizosaccharomyces pombe. The SIN promotes cytokinesis, and the MOR drives cell separation at the end of cytokinesis and polarized growth during interphase. We showed previously that cross talk exists between these two pathways, with the SIN inhibiting the MOR during cytokinesis through phosphorylation of the MOR component Nak1 by the SIN Sid2 kinase. The reason for this inhibition remained uncertain. We show here that failure to inhibit MOR signaling during cytokinesis results in cell lysis at the site of septum formation. Time-lapse analysis revealed that MOR signaling during cytokinesis causes cells to prematurely initiate septum degradation/cell separation. The cell lysis phenotype is due to premature initiation of cell separation because it can be rescued by mutations in genes required for cell separation/septum degradation. We also shed further light on how the SIN inhibits the MOR. Sid2 phosphorylation of the MOR proteins Sog2 and Nak1 is required to prevent cell lysis during cytokinesis. Together, these results show that SIN inhibition of the MOR enforces proper temporal ordering of cytokinetic events.
NDR（核Dbf-2相关）激酶构成信号网络中的关键调控节点，这些信号网络控制着多种生物学过程，如生长、增殖、有丝分裂退出、形态发生和细胞凋亡。在裂殖酵母粟酒裂殖酵母中存在两条名为隔膜起始网络（SIN）和形态发生Orb6网络（MOR）的NDR途径。SIN促进胞质分裂，而MOR在胞质分裂末期驱动细胞分离，并在间期驱动极化生长。我们之前表明这两条途径之间存在相互作用，在胞质分裂期间，SIN通过其Sid2激酶使MOR组分Nak1磷酸化来抑制MOR。这种抑制的原因尚不确定。我们在此表明，在胞质分裂期间未能抑制MOR信号会导致在隔膜形成部位的细胞裂解。延时分析表明，胞质分裂期间的MOR信号会导致细胞过早开始隔膜降解/细胞分离。细胞裂解表型是由于细胞分离过早开始，因为它可以通过细胞分离/隔膜降解所需基因的突变来挽救。我们还进一步阐明了SIN如何抑制MOR。MOR蛋白Sog2和Nak1的Sid2磷酸化是防止胞质分裂期间细胞裂解所必需的。总之，这些结果表明SIN对MOR的抑制作用确保了胞质分裂事件的正确时间顺序。
