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Interaction of heat shock protein 70 with membranes depends on the lipid environment

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Cell Stress and Chaperones Aims and scope

Abstract

Heat shock proteins (hsp) are well recognized for their protein folding activity. Additionally, hsp expression is enhanced during stress conditions to preserve cellular homeostasis. Hsp are also detected outside cells, released by an active mechanism independent of cell death. Extracellular hsp appear to act as signaling molecules as part of a systemic response to stress. Extracellular hsp do not contain a consensus signal for their secretion via the classical ER-Golgi compartment. Therefore, they are likely exported by an alternative mechanism requiring translocation across the plasma membrane. Since Hsp70, the major inducible hsp, has been detected on surface of stressed cells, we propose that membrane interaction is the first step in the export process. The question that emerges is how does this charged cytosolic protein interact with lipid membranes? Prior studies have shown that Hsp70 formed ion conductance pathways within artificial lipid bilayers. These early observations have been extended herewith using a liposome insertion assay. We showed that Hsp70 selectively interacted with negatively charged phospholipids, particularly phosphatidyl serine (PS), within liposomes, which was followed by insertion into the lipid bilayer, forming high-molecular weight oligomers. Hsp70 displayed a preference for less fluid lipid environments and the region embedded into the lipid membrane was mapped toward the C-terminus end of the molecule. The results from our studies provide evidence of an unexpected ability of a large, charged protein to become inserted into a lipid membrane. This observation provides a new paradigm for the interaction of proteins with lipid environments. In addition, it may explain the export mechanism of an increasing number of proteins that lack the consensus secretory signals.

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Acknowledgments

This work was supported by the National Institutes of Health, grant numbers GM R01 098455 and GM R25 083275. We would like to thank Dr. Majid Ghassemian for the mass spectrometry analysis. We are also grateful to Dr. C.C. King for providing us with Hsp70-GST construct. The editorial assistance of Molly Wofford is also appreciated.

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Authors and Affiliations

  1. Initiative for Maximizing Student Development (IMSD) Program, University of California San Diego, La Jolla, CA, USA

    Gabrielle Armijo, Jonathan Okerblom & Victor Lopez

  2. Department of Surgery, School of Medicine, La Jolla, CA, USA

    David M. Cauvi

  3. Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA

    Diana E. Schlamadinger & Judy Kim

  4. Uniformed Services University, Bethesda, MD, USA

    Nelson Arispe

  5. Center for Investigations of Health and Education Disparities, University of California San Diego, La Jolla, CA, USA

    Antonio De Maio

  6. Departments of Surgery and Neuroscience, School of Medicine, University of California San Diego, 9500 Gilman Drive, #0739, La Jolla, 92093-0739, CA, USA

    Antonio De Maio

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  1. Gabrielle Armijo
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  2. Jonathan Okerblom
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  3. David M. Cauvi
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  4. Victor Lopez
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  5. Diana E. Schlamadinger
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  6. Judy Kim
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  7. Nelson Arispe
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  8. Antonio De Maio
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Correspondence to Antonio De Maio.

Additional information

Gabrielle Armijo, Jonathan Okerblom, and David M. Cauvi contributed equally to this project.

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Armijo, G., Okerblom, J., Cauvi, D.M. et al. Interaction of heat shock protein 70 with membranes depends on the lipid environment. Cell Stress and Chaperones 19, 877–886 (2014). https://doi.org/10.1007/s12192-014-0511-x

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  • DOI: https://doi.org/10.1007/s12192-014-0511-x

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