title: Rac1 participates in thermally induced alterations of the cytoskeleton, cell morphology and lipid rafts, and regulates the expression of heat shock proteins in B16F10 melanoma cells.
abstract: Eukaryotic cells exhibit a characteristic response to hyperthermic treatment, involving morphological and cytoskeletal alterations and the induction of heat shock protein synthesis. Small GTPases of the Ras superfamily are known to serve as molecular switches which mediate responses to extracellular stimuli. We addressed here how small GTPase Rac1 integrates signals from heat stress and simultaneously induces various cellular changes in mammalian cells. As evidence that Rac1 is implicated in the heat shock response, we first demonstrated that both mild (41.5°C) and severe (43°C) heat shock induced membrane translocation of Rac1. Following inhibition of the activation or palmitoylation of Rac1, the size of its plasma membrane-bound pool was significantly decreased while the heat shock-induced alterations in the cytoskeleton and cell morphology were prevented. We earlier documented that the size distribution pattern of cholesterol-rich rafts is temperature dependent and hypothesized that this is coupled to the triggering mechanism of stress sensing and signaling. Interestingly, when plasma membrane localization of Rac1 was inhibited, a different and temperature independent average domain size was detected. In addition, inhibition of the activation or palmitoylation of Rac1 resulted in a strongly decreased expression of the genes of major heat shock proteins hsp25 and hsp70 under both mild and severe heat stress conditions.
authors.affiliation: Institute of Biochemistry, Laboratory of Molecular Stress Biology, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Burcin
authors.initials: B
authors.lastname: Gungor
authors.affiliation: Institute of Biochemistry, Laboratory of Molecular Stress Biology, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Gombos
authors.affiliation: Institute of Biochemistry, Laboratory of Molecular Stress Biology, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Tim
authors.initials: T
authors.lastname: Crul
authors.affiliation: Laboratory of Cellular Imaging, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Ferhan
authors.initials: F
authors.lastname: Ayaydin
authors.affiliation: Institute of Material and Environmental Chemistry, Department of Functional and Structural Materials, Research Center for Natural Sciences, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Szabó
authors.affiliation: Institute of Biochemistry, Laboratory of Molecular Stress Biology, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Török
authors.affiliation: Institute of Genetics, Laboratory of Cancer Genome Research, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Mátés
authors.affiliation: Institute of Biochemistry, Laboratory of Molecular Stress Biology, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Vígh
authors.affiliation: Institute of Biochemistry, Laboratory of Molecular Stress Biology, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Horváth
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics*; D018869:Heat-Shock Response; D054878:Lipoylation; D008546:Melanoma, Experimental / Q000473:pathology*; D008560:Membrane Fluidity; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics*; D021381:Protein Transport; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D002784:Cholesterol; D020830:rac1 GTP-Binding Protein