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Evidence on Cholesterol-Controlled Lipid Raft Interaction of the Small Heat Shock Protein HSPB11

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Cellular Trafficking of Cell Stress Proteins in Health and Disease

Part of the book series: Heat Shock Proteins ((HESP,volume 6))

Abstract

Small heat-shock proteins (sHSPs) are members of the family of molecular chaperones. Their major cellular function is considered to be the prevention of irreversible protein aggregation during stress conditions and subsequent promotion of the folding of partially denatured proteins. However, sHSPs may also be associated with biological membranes and participate in cellular “stress management” by acting as membrane-stabilizing factors. In spite of the great potential significance in the development of therapeutic strategies, the mechanisms of the membrane (and lipid) association of sHSPs are still unknown. A novel 16.2 kDa human sHSP, HSPB11, inhibits H2O2, taxol and etoposide-induced cell death through stabilization of the mitochondrial membrane system, the activation of HSP90, the stabilization of lipid rafts and activation of the PI-3-kinase—Akt cytoprotective pathway. We show here that HSPB11 binds to lipid membranes via a specific cholesterol-mediated interaction. The affinity of HSPB11 demonstrates a very distinct cholesterol-dependent binding to cholesterol/sphingomyelin Langmuir monolayers: If the cholesterol concentration increases above a certain level, HSPB11 binds to membranes much more efficiently. The possible roles of HSPB11 and other sHSPs in protection against stress-induced hydrophobic membrane defects are discussed.

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Acknowledgements

This work was supported in part by grants from the Hungarian National Scientific Research Foundation (OTKA K82097 and OTKA K84257) and the Hungarian National Development Agency (TAMOP-4.2.2/08/1-2008-0002, TAMOP-4.2.2/08/1-2008-0013 and TAMOP-4.2.2/08/1-2008-0014).

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Authors and Affiliations

  1. Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt 62, H6726, Szeged, Hungary

    Zsolt Török, Ana-Maria Pilbat, Imre Gombos, Ibolya Horváth & László Vígh

  2. Department of Biochemistry and Medical Chemistry, University of Pécs, Pécs, Hungary

    Enikö Hocsák & Balázs Sümegi

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  1. Zsolt Török
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  2. Ana-Maria Pilbat
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  3. Imre Gombos
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  4. Enikö Hocsák
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  5. Balázs Sümegi
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  6. Ibolya Horváth
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  7. László Vígh
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Correspondence to László Vígh .

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Editors and Affiliations

  1. Eastman Dental Institute, Div. Microbial Diseases, University College, London, Gray's Inn Road 256, London, WC1X 8LD, United Kingdom

    Brian Henderson

  2. School of Medicine & Biomedical Science, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, United Kingdom

    A. Graham Pockley

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Török, Z. et al. (2012). Evidence on Cholesterol-Controlled Lipid Raft Interaction of the Small Heat Shock Protein HSPB11. In: Henderson, B., Pockley, A. (eds) Cellular Trafficking of Cell Stress Proteins in Health and Disease. Heat Shock Proteins, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4740-1_5

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