Hsp90α and Hsp90β together operate a hypoxia and nutrient paucity stress-response mechanism during wound healing

Journal of Cell Science
Priyamvada JayaprakashWei Li

Abstract

When tissues are injured and blood vessels clot, the local environment becomes ischemic, meaning that there is a lack of adequate supply of oxygen and glucose delivered to the surrounding cells. The heat shock protein-90 (Hsp90) family proteins protect tissues from various environmental insults and participate in the repair of damaged tissue. Here, we report discovery of a new ischemia-responsive mechanism in which the two Hsp90 isoforms Hsp90α and Hsp90β (also known as HSP90AA1 and HSP90AB1, respectively) work together to promote cell motility in wounded skin and accelerate wound closure. We demonstrate that Hsp90α and Hsp90β have distinct and non-exchangeable functions during wound healing. Under hypoxia and when there is a lack of serum factors, Hsp90β binds to the cytoplasmic tail of the LDL receptor-related protein-1 (LRP-1) and stabilizes the receptor at the cell surface. Hsp90α, however, is secreted by the cell into extracellular space where it binds and signals through the LRP-1 receptor to promote cell motility, leading to wound closure. In addition to skin injury, we suggest that this repair mechanism applies broadly to other non-cutaneous injured tissues.

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Citations

Feb 15, 2016·Trends in Biochemical Sciences·Stuart K Calderwood, Jianlin Gong
May 21, 2016·Frontiers in Immunology·Stuart K CalderwoodAyesha Murshid
Jul 7, 2016·Molecular Therapy. Methods & Clinical Development·Ayesha BhatiaWei Li
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