title: A Pil1-Sle1-Syj1-Tax4 functional pathway links eisosomes with PI(4,5)P2 regulation.
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.
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Kabeche
authors.forename: Assen
authors.initials: A
authors.lastname: Roguev
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.forename: James B
authors.initials: JB
authors.lastname: Moseley
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008081:Liposomes; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D021381:Protein Transport; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D003598:Cytoskeletal Proteins; D008081:Liposomes; D046912:Multiprotein Complexes; D019269:Phosphatidylinositol 4,5-Diphosphate; C570229:Pil1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases
keywords: Eisosome; PI(4,5)P2; Synaptojanin; TORC2