Presentation Title

Membrane localization of HspA1A, a stress inducible 70-kDa heat shock protein

Faculty Mentor

Nikolas Nikolaidis

Start Date

18-11-2017 12:30 PM

End Date

18-11-2017 1:30 PM

Location

BSC-Ursa Minor 77

Session

Poster 2

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Membrane localization of HspA1A, a stress inducible 70-kDa heat shock protein

Cedra Labanieh, Julianne Zapanta, Nikolas Nikolaidis

Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Computational and Applied Mathematics, California State University Fullerton, Fullerton, CA

HspA1A is an essential orchestrator of cellular homeostasis. Apart from its function as a molecular chaperone, HspA1A also localizes at the plasma membrane (PM) of 90% of tumors, a phenomenon that has been directly linked to the severity of the disease. However, it is currently unknown how HspA1A, a cytosolic protein, is translocated to the PM. We have recently showed that HspA1A interacts with several lipids, including phosphatidylserine (PS), a lipid found primarily in the inner leaflet of the PM during normal cell growth. Taking into account that lipids recruit proteins to the PM, we hypothesized that the interaction of HspA1A with PS allows the chaperone to localize at the PM. To test this hypothesis, we determined the translocation pattern of HspA1A in human cells and also whether the C2 domain of lactadherin (Lact-C2), a known PS-biosensor, inhibits this translocation by competing for binding to PS. Specifically, Hek and HeLa cells were subjected to mild heat-shock and the PM-localized HspA1A was quantified using confocal microscopy and cell surface biotinylation. These experiments revealed that HspA1A’s membrane localization increases after heat-shock and reaches a maximal value at 8 hours during recovery. In the presence of Lact-C2, however, HspA1A’s membrane localization did not show an increase during recovery after heat-shock. Collectively, these results reveal that HspA1A’s membrane localization and anchorage depends on its interaction with PS. This discovery establishes the necessary foundation to elucidate the mechanism that regulates the localization of HspA1A at the PM of several types of cancer cells.

This project was supported by funds from NIH to NN

keywords: heat-shock proteins, lipids, plasma membrane

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Nov 18th, 12:30 PM Nov 18th, 1:30 PM

Membrane localization of HspA1A, a stress inducible 70-kDa heat shock protein

BSC-Ursa Minor 77

Membrane localization of HspA1A, a stress inducible 70-kDa heat shock protein

Cedra Labanieh, Julianne Zapanta, Nikolas Nikolaidis

Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Computational and Applied Mathematics, California State University Fullerton, Fullerton, CA

HspA1A is an essential orchestrator of cellular homeostasis. Apart from its function as a molecular chaperone, HspA1A also localizes at the plasma membrane (PM) of 90% of tumors, a phenomenon that has been directly linked to the severity of the disease. However, it is currently unknown how HspA1A, a cytosolic protein, is translocated to the PM. We have recently showed that HspA1A interacts with several lipids, including phosphatidylserine (PS), a lipid found primarily in the inner leaflet of the PM during normal cell growth. Taking into account that lipids recruit proteins to the PM, we hypothesized that the interaction of HspA1A with PS allows the chaperone to localize at the PM. To test this hypothesis, we determined the translocation pattern of HspA1A in human cells and also whether the C2 domain of lactadherin (Lact-C2), a known PS-biosensor, inhibits this translocation by competing for binding to PS. Specifically, Hek and HeLa cells were subjected to mild heat-shock and the PM-localized HspA1A was quantified using confocal microscopy and cell surface biotinylation. These experiments revealed that HspA1A’s membrane localization increases after heat-shock and reaches a maximal value at 8 hours during recovery. In the presence of Lact-C2, however, HspA1A’s membrane localization did not show an increase during recovery after heat-shock. Collectively, these results reveal that HspA1A’s membrane localization and anchorage depends on its interaction with PS. This discovery establishes the necessary foundation to elucidate the mechanism that regulates the localization of HspA1A at the PM of several types of cancer cells.

This project was supported by funds from NIH to NN

keywords: heat-shock proteins, lipids, plasma membrane