title: Phosphoinositide kinase signaling controls ER-PM cross-talk.
abstract: Membrane lipid dynamics must be precisely regulated for normal cellular function, and disruptions in lipid homeostasis are linked to the progression of several diseases. However, little is known about the sensory mechanisms for detecting membrane composition and how lipid metabolism is regulated in response to membrane stress. We find that phosphoinositide (PI) kinase signaling controls a conserved PDK-TORC2-Akt signaling cascade as part of a homeostasis network that allows the endoplasmic reticulum (ER) to modulate essential responses, including Ca(2+)-regulated lipid biogenesis, upon plasma membrane (PM) stress. Furthermore, loss of ER-PM junctions impairs this protective response, leading to PM integrity defects upon heat stress. Thus PI kinase-mediated ER-PM cross-talk comprises a regulatory system that ensures cellular integrity under membrane stress conditions.
authors: MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom.
authors: Deike J
authors: DJ
authors: Omnus
authors: Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
authors: Andrew G
authors: AG
authors: Manford
authors: MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom.
authors: Jakob M
authors: JM
authors: Bader
authors: Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 c.stefan@ucl.ac.uk sde26@cornell.edu.
authors: Scott D
authors: SD
authors: Emr
authors: MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853 c.stefan@ucl.ac.uk sde26@cornell.edu.
authors: Christopher J
authors: CJ
authors: Stefan
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D050356:Lipid Metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D064413:3-Phosphoinositide-Dependent Protein Kinases; C118385:PKH1 protein, S cerevisiae; C118386:PKH2 protein, S cerevisiae