title: Plasma membranes as heat stress sensors: from lipid-controlled molecular switches to therapeutic applications.
abstract: The classic heat shock (stress) response (HSR) was originally attributed to protein denaturation. However, heat shock protein (Hsp) induction occurs in many circumstances where no protein denaturation is observed. Recently considerable evidence has been accumulated to the favor of the "Membrane Sensor Hypothesis" which predicts that the level of Hsps can be changed as a result of alterations to the plasma membrane. This is especially pertinent to mild heat shock, such as occurs in fever. In this condition the sensitivity of many transient receptor potential (TRP) channels is particularly notable. Small temperature stresses can modulate TRP gating significantly and this is influenced by lipids. In addition, stress hormones often modify plasma membrane structure and function and thus initiate a cascade of events, which may affect HSR. The major transactivator heat shock factor-1 integrates the signals originating from the plasma membrane and orchestrates the expression of individual heat shock genes. We describe how these observations can be tested at the molecular level, for example, with the use of membrane perturbers and through computational calculations. An important fact which now starts to be addressed is that membranes are not homogeneous nor do all cells react identically. Lipidomics and cell profiling are beginning to address the above two points. Finally, we observe that a deregulated HSR is found in a large number of important diseases where more detailed knowledge of the molecular mechanisms involved may offer timely opportunities for clinical interventions and new, innovative drug treatments. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary. Electronic address: tzsolt@brc.hu.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Török
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Tim
authors.initials: T
authors.lastname: Crul
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Salerno, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Maresca
authors.affiliation: Institute of Applied Physics, Vienna University of Technology, Wiedner Hauptstrasse 8-10, 1040 Vienna, Austria.
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Schütz
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, 03550 San Juan de Alicante, Spain.
authors.forename: Felix
authors.initials: F
authors.lastname: Viana
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Dindia
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Salerno, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Piotto
authors.affiliation: Institute of Applied Physics, Vienna University of Technology, Wiedner Hauptstrasse 8-10, 1040 Vienna, Austria.
authors.forename: Mario
authors.initials: M
authors.lastname: Brameshuber
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Balogh
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Péter
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Salerno, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Porta
authors.affiliation: Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Salerno, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Trapani
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Gombos
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Glatz
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Burcin
authors.initials: B
authors.lastname: Gungor
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Begüm
authors.initials: B
authors.lastname: Peksel
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vigh
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Csoboz
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Horváth
authors.affiliation: Department of Biology, University of Waterloo, Waterloo, Ontario, Canada; Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Mathilakath M
authors.initials: MM
authors.lastname: Vijayan
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Medical School, Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Hooper
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK.
authors.forename: John L
authors.initials: JL
authors.lastname: Harwood
authors.affiliation: Institute of Biochemistry, Biological Research Centre of the Hung. Acad. Sci., Szeged H-6726, Hungary. Electronic address: vigh@brc.hu.
authors.forename: László
authors.initials: L
authors.lastname: Vigh
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000628:therapy*
chemical_list: D006360:Heat-Shock Proteins; D008563:Membrane Lipids
keywords: Cell-to-cell heterogeneity; Heat shock response; Lipid raft; Lipidomics; Membrane lipid therapy; Stress hormone; TRP channel