title: Cross talk between NDR kinase pathways coordinates cytokinesis with cell separation in Schizosaccharomyces pombe.
abstract: 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.
authors: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors: Sneha
authors: S
authors: Gupta
authors: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors: Meera
authors: M
authors: Govindaraghavan
authors: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, USA Dannel.McCollum@umassmed.edu.
authors: Dannel
authors: D
authors: McCollum
mesh_terms: D002352:Carrier Proteins / Q000502:physiology; D048749:Cytokinesis; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology; D029702:Schizosaccharomyces pombe Proteins / Q000502:physiology; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C113816:Sid2 protein, S pombe; C500976:Nak1 protein, S pombe; D017346:Protein Serine-Threonine Kinases