Pheromone-induced anisotropy in yeast plasma membrane phosphatidylinositol- 4,5-bisphosphate distribution is required for MAPK signaling Academic Article uri icon


MeSH Major

  • MAP Kinase Signaling System
  • Phosphatidylinositol 4,5-Diphosphate
  • Saccharomyces cerevisiae


  • During response of budding yeast to peptide mating pheromone, the cell becomes markedly polarized and MAPK scaffold protein Ste5 localizes to the resulting projection (shmoo tip). We demonstrated before that this recruitment is essential for sustained MAPK signaling and requires interaction of a pleckstrin homology (PH) domain in Ste5 with phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] in the plasma membrane. Using fluorescently tagged high-affinity probes specific for PtdIns(4,5)P(2), we have now found that this phosphoinositide is highly concentrated at the shmoo tip in cells responding to pheromone. Maintenance of this strikingly anisotropic distribution of PtdIns(4,5)P(2), stable tethering of Ste5 at the shmoo tip, downstream MAPK activation, and expression of a mating pathway-specific reporter gene all require continuous function of the plasma membrane-associated PtdIns 4-kinase Stt4 and the plasma membrane-associated PtdIns4P 5-kinase Mss4 (but not the Golgi-associated PtdIns 4-kinase Pik1). Our observations demonstrate that PtdIns(4,5)P(2) is the primary determinant for restricting localization of Ste5 within the plasma membrane and provide direct evidence that an extracellular stimulus-evoked self-reinforcing mechanism generates a spatially enriched pool of PtdIns(4,5)P(2) necessary for the membrane anchoring and function of a signaling complex.

publication date

  • June 29, 2010



  • Academic Article



  • eng

PubMed Central ID

  • PMC2900652

Digital Object Identifier (DOI)

  • 10.1073/pnas.1005817107

PubMed ID

  • 20547860

Additional Document Info

start page

  • 11805

end page

  • 10


  • 107


  • 26