title: Yeast Integral Membrane Proteins Apq12, Brl1, and Brr6 Form a Complex Important for Regulation of Membrane Homeostasis and Nuclear Pore Complex Biogenesis.
abstract: Proper functioning of intracellular membranes is critical for many cellular processes. A key feature of membranes is their ability to adapt to changes in environmental conditions by adjusting their composition so as to maintain constant biophysical properties, including fluidity and flexibility. Similar changes in the biophysical properties of membranes likely occur when intracellular processes, such as vesicle formation and fusion, require dramatic changes in membrane curvature. Similar modifications must also be made when nuclear pore complexes (NPCs) are constructed within the existing nuclear membrane, as occurs during interphase in all eukaryotes. Here we report on the role of the essential nuclear envelope/endoplasmic reticulum (NE/ER) protein Brl1 in regulating the membrane composition of the NE/ER. We show that Brl1 and two other proteins characterized previously-Brr6, which is closely related to Brl1, and Apq12-function together and are required for lipid homeostasis. All three transmembrane proteins are localized to the NE and can be coprecipitated. As has been shown for mutations affecting Brr6 and Apq12, mutations in Brl1 lead to defects in lipid metabolism, increased sensitivity to drugs that inhibit enzymes involved in lipid synthesis, and strong genetic interactions with mutations affecting lipid metabolism. Mutations affecting Brl1 or Brr6 or the absence of Apq12 leads to hyperfluid membranes, because mutant cells are hypersensitive to agents that increase membrane fluidity. We suggest that the defects in nuclear pore complex biogenesis and mRNA export seen in these mutants are consequences of defects in maintaining the biophysical properties of the NE.
authors.affiliation: Department of Biology, University of Fribourg, Fribourg, Switzerland.
authors.forename: Museer A
authors.initials: MA
authors.lastname: Lone
authors.affiliation: Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Atkinson
authors.affiliation: Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Hodge
authors.affiliation: Department of Biology, University of Fribourg, Fribourg, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cottier
authors.affiliation: Department of Biology, University of Fribourg, Fribourg, Switzerland.
authors.forename: Fernando
authors.initials: F
authors.lastname: Martínez-Montañés
authors.affiliation: Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Shelley
authors.initials: S
authors.lastname: Maithel
authors.affiliation: Department of Biology, University of Fribourg, Fribourg, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mène-Saffrané
authors.affiliation: Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA charles.cole@dartmouth.edu roger.schneiter@unifr.ch.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Cole
authors.affiliation: Department of Biology, University of Fribourg, Fribourg, Switzerland charles.cole@dartmouth.edu roger.schneiter@unifr.ch.
authors.forename: Roger
authors.initials: R
authors.lastname: Schneiter
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D019905:Benzyl Alcohol / Q000494:pharmacology; D004843:Epistasis, Genetic / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D001678:Organelle Biogenesis; D034443:RNA Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013261:Sterols / Q000378:metabolism; D014783:Viscosity
chemical_list: D008563:Membrane Lipids; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D019905:Benzyl Alcohol