Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins

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Issue Date
2016-02-12Author
Ghosh, Suman
Shinogle, Heather E.
Galeva, Nadezhda A.
Dobrowsky, Rick T.
Blagg, Brian S. J.
Publisher
American Society for Biochemistry and Molecular Biology
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© The American Society for Biochemistry and Molecular Biology.
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Show full item recordAbstract
Heat shock protein 90 (HSP90) is a molecular chaperone that is up-regulated in cancer and is required for the folding of numerous signaling proteins. Consequently, HSP90 represents an ideal target for the development of new anti-cancer agents. The human HSP90 isoform, glucose-regulated protein 94 (GRP94), resides in the endoplasmic reticulum and regulates secretory pathways, integrins, and Toll-like receptors, which contribute to regulating immunity and metastasis. However, the cellular function of GRP94 remains underinvestigated. We report that GRP94 knockdown cells are defective in intracellular transport and, consequently, negatively impact the trafficking of F-actin toward the cellular cortex, integrin α2 and integrin αL toward the cell membrane and filopodia, and secretory vesicles containing the HSP90α-AHA1-survivin complex toward the leading edge. As a result, GRP94 knockdown cells form a multipolar spindle instead of bipolar morphology and consequently manifest a defect in cell migration and adhesion.
Description
This research was originally published in the Journal of Biological Chemistry. Suman Ghosh, Heather E. Shinogle, Nadezhda A. Galeva, Rick T. Dobrowsky, and Brian S. J. Blagg. Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose-regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport. Journal of Biological Chemistry. 2016; 291, 8309-8323.
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Citation
Ghosh, S., Shinogle, H. E., Galeva, N. A., Dobrowsky, R. T., & Blagg, B. S. (2016). Endoplasmic reticulum-resident heat shock protein 90 (HSP90) isoform glucose-regulated protein 94 (GRP94) regulates cell polarity and cancer cell migration by affecting intracellular transport. Journal of Biological Chemistry, 291(16), 8309-8323.
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