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.
About the authors

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 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 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 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.
Acknowledgments
We apologize to all of our colleagues, whose work could not be cited. R.E. acknowledges the Deutsche Forschungsgemeinschaft for support (Emmy Noether Program ER608/2-1, SFB807 Transport and Communication across Biological Membranes, and the CEF-II Adjunct Investigator Program). The Pymol Molecular Graphics System was used for the representation of α-helices.
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, 1043–1055.10.1083/jcb.201010111Search in Google Scholar PubMed PubMed Central
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, 16185–16190.10.1073/pnas.0906699106Search in Google Scholar PubMed PubMed Central
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, 3228–3231.10.1128/JB.185.10.3228-3231.2003Search in Google Scholar PubMed PubMed Central
Antonny, B. (2011). Mechanisms of membrane curvature sensing. Annu. Rev. Biochem. 80, 101–123.10.1146/annurev-biochem-052809-155121Search in Google Scholar PubMed
Bigay, J. and Antonny, B. (2012). Curvature, lipid packing, and electrostatics of membrane organelles, defining cellular territories in determining specificity. Dev. Cell 23, 886–895.10.1016/j.devcel.2012.10.009Search in Google Scholar PubMed
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, 1249783.10.1126/science.1249783Search in Google Scholar PubMed
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, 355–368.10.1016/j.cell.2006.08.044Search in Google Scholar PubMed PubMed Central
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, 15313–15318.10.1074/jbc.M213128200Search in Google Scholar PubMed
Chang, Y.F. and Carman, G.M. (2006). Casein kinase II phosphorylation of the yeast phospholipid synthesis transcription factor Opi1p. J. Biol. Chem. 281, 4754–4761.10.1074/jbc.M513064200Search in Google Scholar PubMed PubMed Central
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, 161–166.10.1038/72440Search in Google Scholar PubMed
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, 525–529.10.1038/nature10742Search in Google Scholar PubMed
Coskun, Ü., Grzybek, M., Drechsel, D., and Simons, K. (2011). Regulation of human EGF receptor by lipids. Proc. Natl. Acad. Sci. USA 108, 9044–9048.10.1073/pnas.1105666108Search in Google Scholar PubMed PubMed Central
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, 1539–1544.10.1016/j.cub.2010.06.074Search in Google Scholar PubMed
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, 313–331.10.1111/mmi.12870Search in Google Scholar PubMed
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, 799–805.10.1006/jmbi.2001.5353Search in Google Scholar PubMed
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, 38980–38991.10.1074/jbc.M112.402081Search in Google Scholar PubMed PubMed Central
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, 984–994.10.1016/j.bbamem.2011.08.021Search in Google Scholar PubMed
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, 9933–9945.10.1074/jbc.M112.441493Search in Google Scholar PubMed PubMed Central
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, 2136–2141.10.1073/pnas.0811700106Search in Google Scholar PubMed PubMed Central
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, 257–275.10.1083/jcb.201012028Search in Google Scholar PubMed PubMed Central
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, 639–651.10.1006/jmbi.1999.3126Search in Google Scholar PubMed
Fonseca, S.G., Gromada, J., and Urano, F. (2011). Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol. Metab. 22, 266–274.10.1016/j.tem.2011.02.008Search in Google Scholar PubMed PubMed Central
Gautier, R., Douguet, D., Antonny, B., and Drin, G. (2008). HELIQUEST: A web server to screen sequences with specific α -helical properties. Bioinformatics 24, 2101–2102.10.1093/bioinformatics/btn392Search in Google Scholar PubMed
Goldstein, J.L., DeBose-Boyd, R.A., and Brown, M.S. (2006). Protein sensors for membrane sterols. Cell 124, 35–46.10.1016/j.cell.2005.12.022Search in Google Scholar PubMed
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, 9265–9270.10.1074/jbc.274.14.9265Search in Google Scholar PubMed
Hampton, R.Y. (2002). Proteolysis and sterol regulation. Annu. Rev. Cell Dev. Biol. 18, 345–378.10.1146/annurev.cellbio.18.032002.131219Search in Google Scholar PubMed
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, 9210–9218.10.1074/jbc.M600425200Search in Google Scholar PubMed PubMed Central
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, 5851–5856.10.1073/pnas.0911617107Search in Google Scholar PubMed PubMed Central
Hannun, Y.A. and Obeid, L.M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell Biol. 9, 139–150.10.1038/nrm2329Search in Google Scholar PubMed
Harding, H.P., Zhang, Y., and Ron, D. (1999). Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397, 271–274.10.1038/16729Search in Google Scholar PubMed
Henry, S.A., Kohlwein, S.D., and Carman, G.M. (2012). Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae. Genetics 190, 317–349.10.1534/genetics.111.130286Search in Google Scholar PubMed PubMed Central
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, 452–461.10.1016/j.jmb.2009.11.054Search in Google Scholar PubMed
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, 729–739.10.1016/j.devcel.2014.04.025Search in Google Scholar PubMed PubMed Central
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, 577–586.10.1016/S0092-8674(00)00080-5Search in Google 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, 3579–3584.10.1073/pnas.1317147111Search in Google Scholar PubMed PubMed Central
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, 9208–9214.10.1021/bi7008773Search in Google Scholar PubMed
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, 1693–1697.10.1126/science.1167983Search in Google Scholar PubMed PubMed Central
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, 17539–17544.10.1073/pnas.1007974107Search in Google Scholar PubMed PubMed Central
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, 1–22.10.1091/mbc.e13-01-0021Search in Google Scholar PubMed PubMed Central
Kennedy, E.P. and Weiss, S.B. (1956). The function of cytidine coenzymes in the biosynthesis of phospholipides. J. Biol. Chem. 222, 193–214.10.1016/S0021-9258(19)50785-2Search in 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, e35063.10.1371/journal.pone.0035063Search in Google Scholar PubMed PubMed Central
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, E257.10.1371/journal.pbio.0020257Search in Google Scholar PubMed PubMed Central
Korennykh, A. and Walter, P. (2012). Structural basis of the unfolded protein response. Annu. Rev. Cell Dev. Biol. 28, 251–277.10.1146/annurev-cellbio-101011-155826Search in Google Scholar PubMed
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, 504–515.10.1016/j.cmet.2011.07.013Search in Google Scholar PubMed PubMed Central
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, 525–530.10.1006/jmbi.1996.0595Search in Google Scholar PubMed
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, 192–194.10.1038/nchembio.1733Search in Google Scholar PubMed
Lee, A.G. (2011). Biological membranes: the importance of molecular detail. Trends Biochem. Sci. 36, 493–500.10.1016/j.tibs.2011.06.007Search in Google Scholar PubMed
Lee, C.-H., Olson, P., and Evans, R.M. (2003). Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology 144, 2201–2207.10.1210/en.2003-0288Search in Google Scholar PubMed
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, 1742–1755.10.1074/jbc.M113.526970Search in Google Scholar PubMed PubMed Central
Lemmon, M.A. (2008). Membrane recognition by phospholipid-binding domains. Nat. Rev. Mol. Cell Biol. 9, 99–111.10.1038/nrm2328Search in Google Scholar PubMed
Lemmon, M.A., and Schlessinger, J. (2010). Cell signaling by receptor tyrosine kinases. Cell 141, 1117–1134.10.1016/j.cell.2010.06.011Search in Google Scholar PubMed PubMed Central
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, 22050–22054.10.1073/pnas.1016184107Search in Google Scholar PubMed PubMed Central
Lingwood, D. and Simons, K. (2010). Lipid rafts as a membrane-organizing principle. Science 327, 46–50.10.1126/science.1174621Search in Google Scholar PubMed
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, e104141.10.1371/journal.pone.0104141Search in Google Scholar PubMed PubMed Central
Lin, J.H., Walter, P., and Yen, T.S.B. (2008). Endoplasmic reticulum stress in disease pathogenesis. Annu. Rev. Pathol. 3, 399–425.10.1146/annurev.pathmechdis.3.121806.151434Search in Google Scholar PubMed PubMed Central
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, 245–254.10.1016/j.cmet.2006.07.007Search in Google Scholar PubMed
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, 1644–1647.10.1126/science.1096083Search in Google Scholar PubMed
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, 494–503.10.1021/bi002140rSearch in Google Scholar PubMed
MacKenzie, K.R. (1997). A transmembrane helix dimer: structure and implications. Science 276, 131–133.10.1126/science.276.5309.131Search in Google Scholar PubMed
Marrink, S.J. and Tieleman, D.P. (2013). Perspective on the Martini model. Chem. Soc. Rev. 42, 6801–6822.10.1039/c3cs60093aSearch in Google Scholar PubMed
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, 830–843.10.1016/j.cell.2013.09.056Search in Google Scholar PubMed
Natter, K. and Kohlwein, S.D. (2012). Yeast and cancer cells-common principles in lipid metabolism. Biochim. Biophys. Acta 1831, 314–326.10.1016/j.bbalip.2012.09.003Search in Google Scholar PubMed PubMed Central
Nile, A.H., Bankaitis, V.A., and Grabon, A. (2010). Mammalian diseases of phosphatidylinositol transfer proteins and their homologs. Clin. Lipidol. 5, 867–897.10.2217/clp.10.67Search in Google Scholar PubMed PubMed Central
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, 1165–1175.10.1006/jmbi.1998.2217Search in Google Scholar PubMed
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, 699–709.10.1083/jcb.200407094Search in Google Scholar PubMed PubMed Central
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, 1311–1314.10.1182/blood-2010-08-303099Search in Google Scholar PubMed PubMed Central
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, 673–690.10.1111/j.1600-0854.2009.00903.xSearch in Google Scholar PubMed
Polo, S. and Di Fiore, P.P. (2006). Endocytosis conducts the cell signaling orchestra. Cell 124, 897–900.10.1016/j.cell.2006.02.025Search in Google Scholar PubMed
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, 89–103.10.1083/jcb.201011118Search in Google Scholar PubMed PubMed Central
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, 3520–3532.10.1091/mbc.e11-04-0295Search in 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, 10503–10512.10.1021/bi800678tSearch in Google Scholar PubMed
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, 667–677.10.1016/S0092-8674(01)00595-5Search in 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, 300–307.10.1038/35085509Search in Google Scholar PubMed
Ridder, A., Skupjen, P., Unterreitmeier, S., and Langosch, D. (2005). Tryptophan supports interaction of transmembrane helices. J. Mol. Biol. 354, 894–902.10.1016/j.jmb.2005.09.084Search in Google Scholar PubMed
Ruipérez, V., Darios, F., and Davletov, B. (2010). Alpha-synuclein, lipids and Parkinson’s disease. Prog. Lipid Res. 49, 420–428.10.1016/j.plipres.2010.05.004Search in Google Scholar PubMed
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, 863–868.10.1073/pnas.96.3.863Search in Google Scholar PubMed PubMed Central
Russ, W.P. and Engelman, D.M. (2000). The GxxxG motif: a framework for transmembrane helix-helix association. J. Mol. Biol. 296, 911–919.10.1006/jmbi.1999.3489Search in Google Scholar PubMed
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, 2309–2313.10.1021/bi0356294Search in Google Scholar PubMed
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, 19753–19761.10.1074/jbc.M610368200Search in Google Scholar PubMed
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, 2313–2318.10.1016/j.bbamem.2014.05.006Search in Google Scholar PubMed
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, 1931–1941.10.1038/sj.emboj.7600672Search in Google Scholar PubMed PubMed Central
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, 12257–12264.10.1021/jp901371hSearch in Google Scholar PubMed
Schneider, D. and Engelman, D.M. (2003). GALLEX, a measurement of heterologous association of transmembrane helices in a biological membrane. J. Biol. Chem. 278, 3105–3111.10.1074/jbc.M206287200Search in Google Scholar PubMed
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, 741–754.10.1083/jcb.146.4.741Search in Google Scholar PubMed PubMed Central
Schröder, M. and Kaufman, R.J. (2005). The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739–789.10.1146/annurev.biochem.73.011303.074134Search in Google Scholar PubMed
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, 507–519.10.1016/j.cell.2005.08.031Search in Google Scholar PubMed
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, 921–936.10.1006/jmbi.1999.3488Search in Google Scholar PubMed
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, 9056–9061.10.1073/pnas.161280798Search in Google Scholar PubMed PubMed Central
Sharpe, H.J., Stevens, T.J., and Munro, S. (2010). A comprehensive comparison of transmembrane domains reveals organelle-specific properties. Cell 142, 158–169.10.1016/j.cell.2010.05.037Search in Google Scholar PubMed PubMed Central
Shin, J.J. and Loewen, C.J. (2011). Putting the pH into phosphatidic acid signaling. BMC Biol. 9, 85.10.1186/1741-7007-9-85Search in Google Scholar PubMed PubMed Central
Stordeur, C., Puth, K., Sáenz, J.P., and Ernst, R. (2014). Crosstalk of lipid and protein homeostasis to maintain membrane function. Biol. Chem. 395, 313–326.10.1515/hsz-2013-0235Search in Google Scholar PubMed
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, 519–530.10.1016/j.molcel.2013.06.014Search in Google Scholar PubMed PubMed Central
Tabas, I. and Ron, D. (2011). Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol. 13, 184–190.10.1038/ncb0311-184Search in Google Scholar PubMed PubMed Central
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, 16–27.10.1016/j.molcel.2012.08.016Search in Google Scholar PubMed PubMed Central
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, 5109–5119.10.1038/sj.emboj.7601924Search in Google Scholar PubMed PubMed Central
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, 12726–12732.10.1021/bi00166a003Search in Google Scholar PubMed
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, 275–288.10.1016/j.bbamem.2004.06.010Search in Google Scholar PubMed
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, 112–124.10.1038/nrm2330Search in Google Scholar PubMed PubMed Central
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, 4628–4633.10.1073/pnas.1217611110Search in Google Scholar PubMed PubMed Central
Walters R.F.S. and DeGrado, W.F. (2006). Helix-packing motifs in membrane proteins. Proc. Natl. Acad. Sci. USA 103, 13658–13663.10.1073/pnas.0605878103Search in Google Scholar PubMed PubMed Central
Walter, P. and Ron, D. (2011). The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081–1086.10.1126/science.1209038Search in Google Scholar PubMed
Yadav, R.S. and Tiwari, N.K. (2014). Lipid integration in neurodegeneration: An overview of Alzheimer’s disease. Mol. Neurobiol. 50, 168–176.10.1007/s12035-014-8661-5Search in Google Scholar PubMed
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, 33741–33749.10.1074/jbc.273.50.33741Search in Google Scholar PubMed
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, 1085–1088.10.1126/science.1191026Search in Google Scholar PubMed
©2015 by De Gruyter