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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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Volume 396, Issue 9-10

Issues

Homeostatic control of biological membranes by dedicated lipid and membrane packing sensors

Kristina Puth
  • Institute of Biochemistry, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt/Main, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Harald F. Hofbauer
  • Institute of Biochemistry, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt/Main, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ James P. Sáenz / Robert Ernst
  • Corresponding author
  • Institute of Biochemistry, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt/Main, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-04-03 | DOI: https://doi.org/10.1515/hsz-2015-0130

Abstract

Biological membranes are dynamic and complex assemblies of lipids and proteins. Eukaryotic lipidomes encompass hundreds of distinct lipid species and we have only begun to understand their role and function. This review focuses on recent advances in the field of lipid sensors and discusses methodical approaches to identify and characterize putative sensor domains. We elaborate on the role of integral and conditionally membrane-associated sensor proteins, their molecular mechanisms, and identify open questions in the emerging field of membrane homeostasis.

Keywords: lipid bilayer stress; lipid sensing; membrane homeostasis; membrane stress response; OLE pathway; unfolded protein response (UPR)

References

  • Adeyo, O., Horn, P.J., Lee, S., Binns, D.D., Chandrahas, A., Chapman, K.D., and Goodman, J.M. (2011). The yeast lipin orthologue Pah1p is important for biogenesis of lipid droplets. J. Cell Biol. 192, 1043–1055.Google Scholar

  • Albanesi, D., Martín, M., Trajtenberg, F., Mansilla, M.C., Haouz, A., Alzari, P.M., de Mendoza, D., and Buschiazzo, A. (2009). Structural plasticity and catalysis regulation of a thermosensor histidine kinase. Proc. Natl. Acad. Sci. USA 106, 16185–16190.Google Scholar

  • Altabe, S.G., Aguilar, P., Caballero, G.M., and de Mendoza, D. (2003). The Bacillus subtilis acyl lipid desaturase is a Δ5 desaturase. J. Bacteriol. 185, 3228–3231.Google Scholar

  • Antonny, B. (2011). Mechanisms of membrane curvature sensing. Annu. Rev. Biochem. 80, 101–123.Google Scholar

  • Bigay, J. and Antonny, B. (2012). Curvature, lipid packing, and electrostatics of membrane organelles, defining cellular territories in determining specificity. Dev. Cell 23, 886–895.Google Scholar

  • Brooks, A.J., Dai, W., O’Mara, M.L., Abankwa, D., Chhabra, Y., Pelekanos, R.A., Gardon, O., Tunny, K.A., Blucher, K.M., Morton, C.J., et al. (2014). Mechanism of activation of protein kinase JAK2 by the growth hormone receptor. Science 344, 1249783.Google Scholar

  • Call, M.E., Schnell, J.R., Xu, C., Lutz, R.A., Chou, J.J., and Wucherpfennig, K.W. (2006). The strucutre of the ζ ζ transmembrane dimer reveals features essential for its assembly with the T cell receptor. Cell 127, 355–368.Google Scholar

  • Chandra, S., Chen, X., Rizo, J., Jahn, R., and Südhof, T.C. (2003). A broken α-helix in folded α-synuclein. J. Biol. Chem. 278, 15313–15318.Google Scholar

  • Chang, Y.F. and Carman, G.M. (2006). Casein kinase II phosphorylation of the yeast phospholipid synthesis transcription factor Opi1p. J. Biol. Chem. 281, 4754–4761.Google Scholar

  • Choma, C., Gratkowski, H., Lear, J.D., and DeGrado, W.F. (2000). Asparagine-mediated self-association of a model transmembrane helix. Nat. Struct. Biol. 7, 161–166.Google Scholar

  • Contreras, F.X., Ernst, A.M., Haberkant, P., Björkholm, P., Lindahl, E., Gönen, B., Tischer, C., Elofsson, A., von Heijne, G., Thiele, C., et al. (2012). Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain. Nature 481, 525–529.Google Scholar

  • Coskun, Ü., Grzybek, M., Drechsel, D., and Simons, K. (2011). Regulation of human EGF receptor by lipids. Proc. Natl. Acad. Sci. USA 108, 9044–9048.Google Scholar

  • Cybulski, L.E., Martín, M., Mansilla, M.C., Fernández, A., and de Mendoza, D. (2010). Membrane thickness cue for cold sensing in a bacterium. Curr. Biol. 20, 1539–1544.Google Scholar

  • Danne, L., Aktas, M., Gleichenhagen, J., Grund, N., Wagner, D., Schwalbe, H., Hoffknecht, B., Metzler-Nolte, N., and Narberhaus, F. (2015). Membrane-binding mechanism of a bacterial phospholipid. Mol. Microbiol. 95, 313–331.Google Scholar

  • Dawson, J.P., Weinger, J.S., and Engelman, D.M. (2002). Motifs of serine and threonine can drive association of transmembrane helices. J. Mol. Biol. 316, 799–805.Google Scholar

  • Ding, Z., Taneva, S.G., Huang, H.K.H., Campbell, S.A., Semenec, L., Chen, N., and Cornell, R.B. (2012). A 22-mer segment in the structurally pliable regulatory domain of metazoan CTP, phosphocholine cytidylyltransferase facilitates both silencing and activating functions. J. Biol. Chem. 287, 38980–38991.Google Scholar

  • Domański, J., Marrink, S.J., and Schäfer, L. V. (2012). Transmembrane helices can induce domain formation in crowded model membranes. Biochim. Biophys. Acta Biomembr. 1818, 984–994.Google Scholar

  • Eaton, J.M., Mullins, G.R., Brindley, D.N., and Harris, T.E. (2013). Phosphorylation of lipin 1 and charge on the phosphatidic acid head group control its phosphatidic acid phosphatase activity and membrane association. J. Biol. Chem. 288, 9933–9945.Google Scholar

  • Ejsing, C.S., Sampaio, J.L., Surendranath, V., Duchoslav, E., Ekroos, K., Klemm, R.W., Simons, K., and Shevchenko, A. (2009). Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry. Proc. Natl. Acad. Sci. USA 106, 2136–2141.Google Scholar

  • Fairn, G.D., Schieber, N.L., Ariotti, N., Murphy, S., Kuerschner, L., Webb, R.I., Grinstein, S., and Parton, R.G. (2011). High-resolution mapping reveals topologically distinct cellular pools of phosphatidylserine. J. Cell Biol. 194, 257–275.Google Scholar

  • Fisher, L.E., Engelman, D.M., and Sturgis, J.N. (1999). Detergents modulate dimerization, but not helicity, of the glycophorin A transmembrane domain. J. Mol. Biol. 293, 639–651.Google Scholar

  • Fonseca, S.G., Gromada, J., and Urano, F. (2011). Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol. Metab. 22, 266–274.Google Scholar

  • Gautier, R., Douguet, D., Antonny, B., and Drin, G. (2008). HELIQUEST: A web server to screen sequences with specific α -helical properties. Bioinformatics 24, 2101–2102.Google Scholar

  • Goldstein, J.L., DeBose-Boyd, R.A., and Brown, M.S. (2006). Protein sensors for membrane sterols. Cell 124, 35–46.Google Scholar

  • Gurezka, R., Laage, R., Brosig, B., and Langosch, D. (1999). A Heptad motif of leucine residues found in membrane proteins can drive self-assembly of artificial transmembrane segments. J. Biol. Chem. 274, 9265–9270.Google Scholar

  • Hampton, R.Y. (2002). Proteolysis and sterol regulation. Annu. Rev. Cell Dev. Biol. 18, 345–378.Google Scholar

  • Han, G.-S., Wu, W.-I., and Carman, G.M. (2006). The Saccharomyces cerevisiae Lipin homolog is a Mg2+-dependent phosphatidate phosphatase enzyme. J. Biol. Chem. 281, 9210–9218.Google Scholar

  • Han, S., Lone, M.A., Schneiter, R., and Chang, A. (2010). Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control. Proc. Natl. Acad. Sci. USA 107, 5851–5856.Google Scholar

  • Hannun, Y.A. and Obeid, L.M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 9, 139–150.Google Scholar

  • Harding, H.P., Zhang, Y., and Ron, D. (1999). Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397, 271–274.Google Scholar

  • Henry, S.A., Kohlwein, S.D., and Carman, G.M. (2012). Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae. Genetics 190, 317–349.Google Scholar

  • Herrmann, J.R., Fuchs, A., Panitz, J.C., Eckert, T., Unterreitmeier, S., Frishman, D., and Langosch, D. (2010). Ionic interactions promote transmembrane helix-helix association depending on sequence context. J. Mol. Biol. 396, 452–461.Google Scholar

  • Hofbauer, H.F., Schopf, F.H., Schleifer, H., Knittelfelder, O.L., Pieber, B., Rechberger, G.N., Wolinski, H., Gaspar, M.L., Kappe, C.O., Stadlmann. J., et al. (2014). Regulation of gene expression through a transcriptional repressor that senses acyl-chain length in membrane phospholipids. Dev. Cell 29, 729–739.Google Scholar

  • Hoppe, T., Matuschewski, K., Rape, M., Schlenker, S., Ulrich, H.D., and Jentsch, S. (2000). Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing. Cell 102, 577–586.CrossrefGoogle Scholar

  • Inda, M.E., Vandenbranden, M., Fernández, A., de Mendoza, D., Ruysschaert, J.-M., and Cybulski, L.E. (2014). A lipid-mediated conformational switch modulates the thermosensing activity of DesK. Proc. Natl. Acad. Sci. USA 111, 3579–3584.Google Scholar

  • Johnson, R.M., Hecht, K., and Deber, C.M. (2007). Aromatic and cation-pi interactions enhance helix-helix association in a membrane environment. Biochemistry 46, 9208–9214.Google Scholar

  • Jonikas, M., Collins, S., Denic, V., Oh, E., Quan, E., Schmid, V., Weibezahn, J., Schwappach, B., Walter, P., Weissman, J.S., et al. (2009). Comprehensive characterization of genes required for protein folding in the ER. Science 323, 1693–1697.Google Scholar

  • Karanasios, E., Han, G.-S., Xu, Z., Carman, G.M., and Siniossoglou, S. (2010). A phosphorylation-regulated amphipathic helix controls the membrane translocation and function of the yeast phosphatidate phosphatase. Proc. Natl. Acad. Sci. USA 107, 17539–17544.Google Scholar

  • Karanasios, E., Barbosa, A.D., Sembongi, H., Mari, M., Han, G.-S., Reggiori, F., Carman, G.M., and Siniossoglou, S. (2013). Regulation of lipid droplet and membrane biogenesis by the acidic tail of the phosphatidate phosphatase Pah1p. Mol. Biol. Cell 24, 1–22.Google Scholar

  • Kennedy, E.P. and Weiss, S.B. (1956). The function of cytidine coenzymes in the biosynthesis of phospholipides. J. Biol. Chem. 222, 193–214.Google Scholar

  • Klose, C., Surma, M.A., Gerl, M.J., Meyenhofer, F., Shevchenko, A., and Simons, K. (2012). Flexibility of a eukaryotic lipidome-insights from yeast lipidomics. PLoS One 7, e35063.Google Scholar

  • Kniazeva, M., Crawford, Q.T., Seiber, M., Wang, C.-Y., and Han, M. (2004). Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development. PLoS Biol. 2, E257.CrossrefGoogle Scholar

  • Korennykh, A. and Walter, P. (2012). Structural basis of the unfolded protein response. Annu. Rev. Cell Dev. Biol. 28, 251–277.Google Scholar

  • Krahmer, N., Guo, Y., Wilfling, F., Hilger, M., Lingrell, S., Heger, K., Newman, H.W., Schmidt-Supprian, M., Vance, D.E., Mann, M., et al. (2011). Phosphatidylcholine synthesis for lipid droplet expansion is mediated by localized activation of CTP:phosphocholine cytidylyltransferase. Cell Metab. 14, 504–515.Google Scholar

  • Langosch, D., Brosig, B., Kolmar, H., and Fritz, H.J. (1996). Dimerisation of the glycophorin A transmembrane segment in membranes probed with the ToxR transcription activator. J. Mol. Biol. 263, 525–530.Google Scholar

  • Larsen, J.B., Jensen, M.B., Bhatia, V.K., Pedersen, S.L., Bjørnholm, T., Iversen, L., Uline, M., Szleifer, I., Jensen, K.J., Hatzakis, N.S., et al. (2015). Membrane curvature enables N-ras lipid anchor sorting to liquid-ordered membrane phases. Nat. Chem. Biol. 11, 192–194.Google Scholar

  • Lee, A.G. (2011). Biological membranes: the importance of molecular detail. Trends Biochem. Sci. 36, 493–500.Google Scholar

  • Lee, C.-H., Olson, P., and Evans, R.M. (2003). Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology 144, 2201–2207.Google Scholar

  • Lee, J., Taneva, S.G., Holland, B.W., Tieleman, D.P., and Cornell, R.B. (2014). Structural basis for autoinhibition of CTP:phosphocholine cytidylyltransferase (CCT), the regulatory enzyme in phosphatidylcholine synthesis, by its membrane-binding amphipathic helix. J. Biol. Chem. 289, 1742–1755.Google Scholar

  • Lemmon, M.A. (2008). Membrane recognition by phospholipid-binding domains. Nat. Rev. Mol. Cell Biol. 9, 99–111.Google Scholar

  • Lemmon, M.A., and Schlessinger, J. (2010). Cell signaling by receptor tyrosine kinases. Cell 141, 1117–1134.Google Scholar

  • Levental, I., Lingwood, D., Grzybek, M., Coskun, U., and Simons, K. (2010). Palmitoylation regulates raft affinity for the majority of integral raft proteins. Proc. Natl. Acad. Sci. USA 107, 22050–22054.Google Scholar

  • Lingwood, D. and Simons, K. (2010). Lipid rafts as a membrane-organizing principle. Science 327, 46–50.Google Scholar

  • Lin, J.-L. and Wheeldon, I. (2014). Dual N- and C-terminal helices are required for endoplasmic reticulum and lipid droplet association of alcohol acetyltransferases in Saccharomyces cerevisiae. PLoS One 9, e104141.Google Scholar

  • Lin, J.H., Walter, P., and Yen, T.S.B. (2008). Endoplasmic reticulum stress in disease pathogenesis. Annu. Rev. Pathol. 3, 399–425.CrossrefGoogle Scholar

  • Lipson, K.L., Fonseca, S.G., Ishigaki, S., Nguyen, L.X., Foss, E., Bortell, R., Rossini, A.A., and Urano, F. (2006). Regulation of insulin biosynthesis in pancreatic b cells by an endoplasmic reticulum-resident protein kinase IRE1. Cell Metab. 4, 245–254.Google Scholar

  • Loewen, C.J.R., Gaspar, M.L., Jesch, S.A., Delon, C., Ktistakis, N.T., Henry, S.A., and Levine, T.P. (2004). Phospholipid metabolism regulated by a transcription factor sensing phosphatidic acid. Science 304, 1644–1647.Google Scholar

  • Lykidis, A., Jackson, P., and Jackowski, S. (2001). Lipid activation of CTP:phosphocholine cytidylyltransferase α: characterization and identification of a second activation domain. Biochemistry 40, 494–503.Google Scholar

  • MacKenzie, K.R. (1997). A transmembrane helix dimer: structure and implications. Science 276, 131–133.Google Scholar

  • Marrink, S.J. and Tieleman, D.P. (2013). Perspective on the Martini model. Chem. Soc. Rev. 42, 6801–6822.Google Scholar

  • Mesmin, B., Bigay, J., Moser Von Filseck, J., Lacas-Gervais, S., Drin, G., and Antonny, B. (2013). A four-step cycle driven by PI4P hydrolysis directs sterol/PI(4)P exchange by the ER-Golgi tether OSBP. Cell 155, 830–843.Google Scholar

  • Natter, K. and Kohlwein, S.D. (2012). Yeast and cancer cells-common principles in lipid metabolism. Biochim. Biophys. Acta 1831, 314–326.Google Scholar

  • Nile, A.H., Bankaitis, V.A., and Grabon, A. (2010). Mammalian diseases of phosphatidylinositol transfer proteins and their homologs. Clin. Lipidol. 5, 867–897.Google Scholar

  • Nilsson, I., Sääf, A., Whitley, P., Gafvelin, G., Waller, C., and von -Heijne, G. (1998). Proline-induced disruption of a transmembrane a-helix in its natural environment. J. Mol. Biol. 284, 1165–1175.Google Scholar

  • Paladino, S., Sarnataro, D., Pillich, R., Tivodar, S., Nitsch, L., and Zurzolo, C. (2004). Protein oligomerization modulates raft partitioning and apical sorting of GPI-anchored proteins. J. Cell Biol. 167, 699–709.Google Scholar

  • Papandreou, I., Denko, N.C., Olson, M., van Melckebeke, H., Lust, S., Tam, A., Solow-Cordero, D.E., Bouley, D.M., Offner, F., Niwa, M., et al. (2011). Identification of an Ire1a endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood 117, 1311–1314.Google Scholar

  • Pineau, L., Colas, J., Dupont, S., Beney, L., Fleurat-Lessard, P., Berjeaud, J.-M., Bergès, T., Ferreira, T. (2009). Lipid-induced ER stress, synergistic effects of sterols and saturated fatty acids. Traffic 10, 673–690.Google Scholar

  • Polo, S. and Di Fiore, P.P. (2006). Endocytosis conducts the cell signaling orchestra. Cell 124, 897–900.Google Scholar

  • Pranke, I.M., Morello, V., Bigay, J., Gibson, K., Verbavatz, J.-M., Antonny, B., and Jackson, C.L. (2011). α-Synuclein and ALPS motifs are membrane curvature sensors whose contrasting chemistry mediates selective vesicle binding. J. Cell Biol. 194, 89–103.Google Scholar

  • Promlek, T., Ishiwata-Kimata, Y., Shido, M., Sakuramoto, M., Kohno, K., and Kimata, Y. (2011). Membrane aberrancy and unfolded proteins activate the endoplasmic reticulum stress sensor Ire1 in different ways. Mol. Biol. Cell 22, 3520–3532.Google Scholar

  • Psachoulia, E., Fowler, P.W., Bond, P.J., and Sansom, M.S. (2008). Helix-helix interactions in membrane proteins: coarse-grained simulations of glycophorin a helix dimerization. Biochemistry 47, 10503–10512.CrossrefGoogle Scholar

  • Rape, M., Hoppe, T., Gorr, I., Kalocay, M., Richly, H., and Jentsch, S. (2001). Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell 107, 667–677.Google Scholar

  • Reimold, A.M., Iwakoshi, N.N., Manis, J., Vallabhajosyula, P., Szomolanyi-Tsuda, E., Gravallese, E.M., Friend, D., Grusby, M.J., Alt, F., and Glimcher, L.H. (2001). Plasma cell differentiation requires the transcription factor XBP-1. Nature 412, 300–307.Google Scholar

  • Ridder, A., Skupjen, P., Unterreitmeier, S., and Langosch, D. (2005). Tryptophan supports interaction of transmembrane helices. J. Mol. Biol. 354, 894–902.Google Scholar

  • Ruipérez, V., Darios, F., and Davletov, B. (2010). Alpha-synuclein, lipids and Parkinson’s disease. Prog. Lipid Res. 49, 420–428.CrossrefGoogle Scholar

  • Russ, W.P. and Engelman, D.M. (1999). TOXCAT: a measure of transmembrane helix association in a biological membrane. Proc. Natl. Acad. Sci. USA 96, 863–868.Google Scholar

  • Russ, W.P. and Engelman, D.M. (2000). The GxxxG motif: a framework for transmembrane helix-helix association. J. Mol. Biol. 296, 911–919.Google Scholar

  • Sal-Man, N., Gerber, D., and Shai, Y. (2004). The composition rather than position of polar residues (QxxS) drives aspartate receptor transmembrane domain dimerization in vivo. Biochemistry 43, 2309–2313.Google Scholar

  • Sal-Man, N., Gerber, D., Bloch, I., and Shai, Y. (2007). Specificity in transmembrane helix-helix interactions mediated by aromatic residues. J. Biol. Chem. 282, 19753–19761.Google Scholar

  • Sal-Man, N., Gerber, D., and Shai, Y. (2014). Proline localized to the interaction interface can mediate self-association of transmembrane domains. Biochim. Biophys. Acta. 1838, 2313–2318.Google Scholar

  • Santos-Rosa, H., Leung, J., Grimsey, N., Peak-Chew, S., and Siniossoglou, S. (2005). The yeast lipin Smp2 couples phospholipid biosynthesis to nuclear membrane growth. EMBO J. 24, 1931–1941.Google Scholar

  • Scarpelli, F., Drescher, M., Rutters-Meijneke, T., Holt, A., Rijkers, D.T.S., Killian, J.A., and Huber, M. (2009). Aggregation of transmembrane peptides studied by spin-label EPR. J. Phys. Chem. B 113, 12257–12264.Google Scholar

  • Schneider, D. and Engelman, D.M. (2003). GALLEX, a measurement of heterologous association of transmembrane helices in a biological membrane. J. Biol. Chem. 278, 3105–3111.Google Scholar

  • Schneiter, R., Brügger, B., Sandhoff, R., Zellnig, G., Leber, A., Lampl, M., Athenstaedt, K., Hrastnik, C., Eder, S., Daum, G., et al. (1999). Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species en route to the plasma membrane. J. Cell Biol. 146, 741–754.Google Scholar

  • Schröder, M. and Kaufman, R.J. (2005). The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739–789.Google Scholar

  • Schuldiner, M., Collins, S.R., Thompson, N.J., Denic, V., Bhamidipati, A., Punna, T., Ihmels, J., Andrews, B., Boone, C., Greenblatt, J.F., et al. (2005). Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell 123, 507–519.Google Scholar

  • Senes, A., Gerstein, M., and Engelman, D.M. (2000). Statistical analysis of amino acid patterns in transmembrane helices: the GxxxG motif occurs frequently and in association with β-branched residues at neighboring positions. J. Mol. Biol. 296, 921–936.Google Scholar

  • Senes, A., Ubarretxena-Belandia, I., and Engelman, D.M. (2001). The Cα---H...O hydrogen bond: a determinant of stability and specificity in transmembrane helix interactions. Proc. Natl. Acad. Sci. USA 98, 9056–9061.Google Scholar

  • Sharpe, H.J., Stevens, T.J., and Munro, S. (2010). A comprehensive comparison of transmembrane domains reveals organelle-specific properties. Cell 142, 158–169.Google Scholar

  • Shin, J.J. and Loewen, C.J. (2011). Putting the pH into phosphatidic acid signaling. BMC Biol. 9, 85.Google Scholar

  • Stordeur, C., Puth, K., Sáenz, J.P., and Ernst, R. (2014). Crosstalk of lipid and protein homeostasis to maintain membrane function. Biol. Chem. 395, 313–326.Google Scholar

  • Surma, M.A., Klose, C., Peng, D., Shales, M., Mrejen, C., Stefanko, A., Braberg, H., Gordon, D.E., Vorkel, D., Ejsing, C.S., et al. (2013). Article A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress. Mol. Cell 51, 519–530.Google Scholar

  • Tabas, I. and Ron, D. (2011). Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol. 13, 184–190.Google Scholar

  • Thibault, G., Shui, G., Kim, W., Mcalister, G.C., Ismail, N., Gygi, S.P., Wenk, M.R., and Ng, D.T. (2012). The membrane stress response buffers lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network. Mol. Cell. 48, 16–27.CrossrefGoogle Scholar

  • Tiwari, R., Köffel, R., and Schneiter, R. (2007). An acetylation/deacetylation cycle controls the export of sterols and steroids from S. cerevisiae. EMBO J. 26, 5109–5119.Google Scholar

  • Treutlein, H.R., Lemmon, M.A., Engelman, D.M., and Brünger, A.T. (1992). The glycophorin A transmembrane domain dimer: sequence-specific propensity for a right-handed supercoil of helices. Biochemistry 31, 12726–12732.Google Scholar

  • Van den Brink-Van Der Laan, E., Killian, J.A., and deKruijff, B. (2004). Nonbilayer lipids affect peripheral and integral membrane proteins via changes in the lateral pressure profile. Biochim. Biophys. Acta Biomembr. 1666, 275–288.Google Scholar

  • Van Meer, G., Voelker, D.R., and Feigenson, G.W. (2008). Membrane lipids: where they are and how they behave. Nat. Rev. Mol. Cell Biol. 9, 112–124.Google Scholar

  • Volmer, R., van der Ploeg, K., and Ron, D. (2013). Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. Proc. Natl. Acad. Sci. USA 110, 4628–4633.Google Scholar

  • Walters R.F.S. and DeGrado, W.F. (2006). Helix-packing motifs in membrane proteins. Proc. Natl. Acad. Sci. USA 103, 13658–13663.Google Scholar

  • Walter, P. and Ron, D. (2011). The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081–1086.Google Scholar

  • Yadav, R.S. and Tiwari, N.K. (2014). Lipid integration in neurodegeneration: An overview of Alzheimer’s disease. Mol. Neurobiol. 50, 168–176.Google Scholar

  • Yoshida, H., Haze, K., Yanagi, H., Yura, T., and Mori, K. (1998). Identification of the cis-Acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. J. Biol. Chem. 273, 33741–33749.Google Scholar

  • Young, B.P., Shin, J.J.H., Orij, R., Chao, J.T., Li, S.C., Guan, X.L., Khong, A., Jan, E., Wenk, M.R., Prinz, W.A., et al. (2010). Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism. Science 329, 1085–1088.Google Scholar

About the article

Kristina Puth

Kristina Puth studied Biochemistry at the Goethe University Frankfurt and received her Diploma in 2012. Since 2012, she has been a PhD student in the Molecular Membrane Biology group at the Goethe University Frankfurt and had focused her PhD on the molecular basis of lipid-induced ER-stress responses.

Harald F. Hofbauer

Harald F. Hofbauer studied Biochemistry and Molecular Biology at the University of Graz. He received his PhD in 2012 in the group of Sepp D. Kohlwein for his research on obese yeast model scenarios, which was partly performed in the laboratory of Susan A. Henry at Cornell University, Ithaca. He then continued as a PostDoc at the University of Graz in the field of lipotoxicity. In October 2014 he joined the group of Robert Ernst at Goethe University, Frankfurt, focusing on lipid-protein interactions at biological membranes.

James P. Sáenz

James P. Sáenz received his PhD from the MIT-WHOI Joint Program in Chemical Oceanography and is presently a postdoctoral fellow at the MPICBG in the group of Prof. Kai Simons. James’ research interests address the natural history and evolution of the membrane and center on understanding the evolutionary basis for lipid structural diversity. For his postdoctoral research he is studying the properties and functions of a class of bacterial ‘sterol surrogates’ called hopanoids.

Robert Ernst

Robert Ernst received his PhD from the University of Düsseldorf. In his postdoctoral phase at the Whitehead Institute for Biomedical research, he studied mechanisms of protein quality control and degradation. He then moved to the laboratory of Kai Simons to study the crosstalk of lipid and protein homeostasis. Since 2012, he has been an Emmy Noether fellow and junior professor for Molecular Membrane Biology at the Goethe University Frankfurt. In 2014 his group moved to the Buchmann Institute for Molecular Life Sciences.


Corresponding author: Robert Ernst, Institute of Biochemistry, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue-Str. 15, D-60438 Frankfurt/Main, Germany, e-mail:

aKristina Puth and Harald F. Hofbauer: These authors contributed equally to this work.


Received: 2015-02-18

Accepted: 2015-03-31

Published Online: 2015-04-03

Published in Print: 2015-09-01


Citation Information: Biological Chemistry, Volume 396, Issue 9-10, Pages 1043–1058, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2015-0130.

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