A Pil1-Sle1-Syj1-Tax4 functional pathway links eisosomes with PI(4,5)P_2 regulation

摘要

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 Pill 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)P_2] in cells. Defects in PI(4,5)P_2 regulation led to eisosome defects, and we found that the core eisosome protein Pill can bind to and tubulate liposomes containing PI(4,5)P_2. Mutations in components of the Pill-SIe1-Syj1-Tax4 pathway suppress the growth and morphology defects of TORC2 mutants, indicating that eisosome-dependent regulation of PI(4,5)P_2 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.