AMPK phosphorylation by Ssp1 is required for proper sexual differentiation in fission yeast

J Cell Sci. 2012 Jun 1;125(Pt 11):2655-64. doi: 10.1242/jcs.098533. Epub 2012 Feb 28.

Abstract

The AMP-activated protein kinase (AMPK) is a central regulator of cellular energy homeostasis, which, in response to a fall in intracellular ATP levels, activates energy-producing pathways and inhibits energy-consuming processes. Here, we report that fission yeast cells lacking AMPK activity are unable to advance entry into mitosis in response to nitrogen starvation and cannot undergo proper G1 arrest and cell differentiation. We also show that AMPK is important in the promotion of the nuclear localization and accumulation of the Ste11 transcription factor. As in animal cells, the fission yeast CaMKK ortholog (Ssp1) phosphorylates and activates the catalytic subunit of AMPK (Ssp2) in its activation loop (Thr189) when cells are starved for nitrogen or glucose. Interestingly, we found that the phosphorylation of Ssp2 on Thr189 is required for nuclear accumulation of AMPK. Our data demonstrate the existence of a signal transduction pathway activated by nutrient starvation that triggers Ssp2 phosphorylation and AMPK redistribution from the cytoplasm to the nucleus. This pathway is important to advance fission cells into mitosis and to establish a timely pre-Start G1 cell cycle arrest for mating.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Enzyme Activation / drug effects
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • HSP70 Heat-Shock Proteins / metabolism*
  • Models, Biological
  • Mutation / genetics
  • Nitrogen / deficiency
  • Nitrogen / pharmacology
  • Phosphorylation / drug effects
  • Phosphothreonine / metabolism
  • Protein Transport / drug effects
  • Protein-Serine-Threonine Kinases / metabolism*
  • Schizosaccharomyces / cytology*
  • Schizosaccharomyces / drug effects
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / growth & development
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Stress, Physiological / drug effects
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / enzymology
  • Transcription Factors / metabolism

Substances

  • HSP70 Heat-Shock Proteins
  • PSS1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • Phosphothreonine
  • ste11 protein, S pombe
  • Protein-Serine-Threonine Kinases
  • Ssp2 protein, S pombe
  • AMP-Activated Protein Kinases
  • Nitrogen