title: Dynamic formation of ER-PM junctions presents a lipid phosphatase to regulate phosphoinositides.
abstract: Endoplasmic reticulum-plasma membrane (ER-PM) contact sites play an integral role in cellular processes such as excitation-contraction coupling and store-operated calcium entry (SOCE). Another ER-PM assembly is one tethered by the extended synaptotagmins (E-Syt). We have discovered that at steady state, E-Syt2 positions the ER and Sac1, an integral ER membrane lipid phosphatase, in discrete ER-PM junctions. Here, Sac1 participates in phosphoinositide homeostasis by limiting PM phosphatidylinositol 4-phosphate (PI(4)P), the precursor of PI(4,5)P2 Activation of G protein-coupled receptors that deplete PM PI(4,5)P2disrupts E-Syt2-mediated ER-PM junctions, reducing Sac1's access to the PM and permitting PM PI(4)P and PI(4,5)P2to recover. Conversely, depletion of ER luminal calcium and subsequent activation of SOCE increases the amount of Sac1 in contact with the PM, depleting PM PI(4)P. Thus, the dynamic presence of Sac1 at ER-PM contact sites allows it to act as a cellular sensor and controller of PM phosphoinositides, thereby influencing many PM processes.
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195 dickson2@uw.edu.
authors.forename: Eamonn J
authors.initials: EJ
authors.lastname: Dickson
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
authors.forename: Jill B
authors.initials: JB
authors.lastname: Jensen
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
authors.forename: Oscar
authors.initials: O
authors.lastname: Vivas
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
authors.forename: Martin
authors.initials: M
authors.lastname: Kruse
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
authors.forename: Alexis E
authors.initials: AE
authors.lastname: Traynor-Kaplan
authors.affiliation: Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195.
authors.forename: Bertil
authors.initials: B
authors.lastname: Hille
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050857:Synaptotagmins / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C037178:phosphatidylinositol 4-phosphate; D050857:Synaptotagmins; D010744:Phosphoric Monoester Hydrolases; D002118:Calcium