A Pil1-Sle1-Syj1-Tax4 functional pathway links eisosomes with PI(4,5)P2 regulation

J Cell Sci. 2014 Mar 15;127(Pt 6):1318-26. doi: 10.1242/jcs.143545. Epub 2014 Jan 16.

Abstract

Stable compartments of the plasma membrane promote a wide range of cellular functions. In yeast cells, cytosolic structures called eisosomes generate prominent cortical invaginations of unknown function. Through a series of genetic screens in fission yeast, we found that the eisosome proteins Pil1 and Sle1 function with the synaptojanin-like lipid phosphatase Syj1 and its ligand Tax4. This genetic pathway connects eisosome function with the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] in cells. Defects in PI(4,5)P2 regulation led to eisosome defects, and we found that the core eisosome protein Pil1 can bind to and tubulate liposomes containing PI(4,5)P2. Mutations in components of the Pil1-Sle1-Syj1-Tax4 pathway suppress the growth and morphology defects of TORC2 mutants, indicating that eisosome-dependent regulation of PI(4,5)P2 feeds into signal transduction pathways. We propose that the geometry of membrane invaginations generates spatial and temporal signals for lipid-mediated signaling events in cells.

Keywords: Eisosome; PI(4,5)P2; Synaptojanin; TORC2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Liposomes
  • Mechanistic Target of Rapamycin Complex 2
  • Multiprotein Complexes / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Protein Transport
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Adaptor Proteins, Vesicular Transport
  • Cytoskeletal Proteins
  • Liposomes
  • Multiprotein Complexes
  • Phosphatidylinositol 4,5-Diphosphate
  • Pil1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 2