The nuclear kinase Lsk1p positively regulates the septation initiation network and promotes the successful completion of cytokinesis in response to perturbation of the actomyosin ring in Schizosaccharomyces pombe

Mol Biol Cell. 2005 Jan;16(1):358-71. doi: 10.1091/mbc.e04-06-0502. Epub 2004 Nov 10.

Abstract

Cytokinesis in fission yeast requires the function of an actomyosin-based contractile ring whose constriction is dependent on a signaling module termed the septation initiation network (SIN). In response to minor perturbation of the ring, the duration of SIN signaling is extended concurrently with a delay in nuclear cycle progression. These mechanisms require the conserved phosphatase Clp1p/Flp1p and facilitate the successful completion of cytokinesis, thereby increasing cellular viability. To isolate novel components of this cytokinesis monitoring system, we screened a genome-wide bank of protein kinase deletion mutants and identified Lsk1p, a nuclear-localized protein kinase. Similar to clp1Delta mutants, and in contrast to wild type, lsk1Delta cells are unable to maintain the integrity of the actomyosin ring upon treatment with low doses (0.3 microM) of latrunculin A. However, unlike clp1Delta mutants, lsk1Delta cells are competent to delay nuclear cycle progression after cytokinetic failure. In addition, lsk1Delta mutants suppress the lethal, multiseptate phenotype conferred by hyperactivation of the SIN, demonstrating that Lsk1p is a positive regulator of this module. In this report, we demonstrate that Lsk1p acts in parallel to Clp1p to promote actomyosin ring stability upon checkpoint activation. Our studies also establish that actomyosin ring maintenance and nuclear cycle delay in response to cytokinetic perturbation can be genetically resolved into independent pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / chemistry
  • Alleles
  • Amino Acid Sequence
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Cycle
  • Cell Nucleus / enzymology*
  • Cell Nucleus / metabolism
  • Cell Survival
  • Cyclin-Dependent Kinases
  • Cytokinesis
  • Dose-Response Relationship, Drug
  • Gene Deletion
  • Genotype
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / metabolism
  • Microscopy, Fluorescence
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / metabolism*
  • Open Reading Frames
  • Phenotype
  • Phylogeny
  • Protein Kinases / biosynthesis
  • Protein Kinases / genetics*
  • Protein Kinases / physiology*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces pombe Proteins / biosynthesis
  • Schizosaccharomyces pombe Proteins / genetics*
  • Schizosaccharomyces pombe Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Temperature
  • Thiazoles / pharmacology
  • Thiazolidines
  • Time Factors

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Schizosaccharomyces pombe Proteins
  • Thiazoles
  • Thiazolidines
  • Green Fluorescent Proteins
  • Actomyosin
  • Protein Kinases
  • Cyclin-Dependent Kinases
  • Lsk1 protein, S pombe
  • latrunculin A