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Identification and molecular mechanisms of the rapid tonicity-induced relocalization of aquaporin 4
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Kitchen, Philip, Day, Rebecca E., Taylor, Luke H. J., Salman, Mootaz M., Bill, Roslyn M., Conner, Matthew T. and Conner, Alex C. (2015) Identification and molecular mechanisms of the rapid tonicity-induced relocalization of aquaporin 4. Journal of Biological Chemistry, 290 . pp. 16873-16881. doi:10.1074/jbc.M115.646034 ISSN 0021-9258.
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Official URL: http://dx.doi.org/10.1074/jbc.M115.646034
Abstract
The aquaporin family of integral membrane proteins is comprised of channels that mediate cellular water flow. Aquaporin 4 (AQP4) is highly expressed in the glial cells of the central nervous system and facilitates the osmotically-driven pathological brain swelling associated with stroke and traumatic brain injury. Here we show that AQP4 cell surface expression can be rapidly and reversibly regulated in response to changes of tonicity in primary cortical rat astrocytes and in transfected HEK293 cells. The translocation mechanism involves protein kinase A (PKA) activation, influx of extracellular calcium and activation of calmodulin. We identify five putative PKA phosphorylation sites and use site-directed mutagenesis to show that only phosphorylation at one of these sites, serine- 276, is necessary for the translocation response. We discuss our findings in the context of the identification of new therapeutic approaches to treating brain oedema.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||
Journal or Publication Title: | Journal of Biological Chemistry | ||||||
Publisher: | American Society for Biochemistry and Molecular Biology | ||||||
ISSN: | 0021-9258 | ||||||
Official Date: | 3 July 2015 | ||||||
Dates: |
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Volume: | 290 | ||||||
Page Range: | pp. 16873-16881 | ||||||
DOI: | 10.1074/jbc.M115.646034 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
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Open Access Version: |
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