Identification and molecular mechanisms of the rapid tonicity-induced relocalization of the aquaporin 4 channel

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.

Publication DOI: https://doi.org/10.1074/jbc.M115.646034
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: Final version free via Creative Commons CC-BY NC ND license. Funding: EPSRC Grant EP/F500378/1.
Uncontrolled Keywords: aquaporin,astrocyte,homeostasis,protein translocation,water channel,hypotonicity,rapid trafficking,regulation,Biochemistry,Cell Biology,Molecular Biology
Publication ISSN: 1083-351X
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.jbc ... 0242-X/fulltext (Publisher URL)
PURE Output Type: Article
Published Date: 2015-07-03
Published Online Date: 2015-05-26
Authors: Kitchen, Philip (ORCID Profile 0000-0002-1558-4673)
Day, Rebecca E.
Taylor, Luke H.J.
Salman, Mootaz M.
Bill, Roslyn M. (ORCID Profile 0000-0003-1331-0852)
Conner, Matthew T.
Conner, Alex C.

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License: Creative Commons Attribution


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