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

KITCHEN, Philip, DAY, Rebecca, TAYLOR, Luke, SALMAN, Mootaz, BILL, Ros, CONNER, Matthew and CONNER, Alex (2015). Identification and molecular mechanisms of the rapid tonicity-induced relocalization of aquaporin 4 channel. Journal of Biological Chemistry, 290 (27), 16873-16881.

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Official URL: JBC: http://intl.jbc.org
Link to published version:: 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: Article
Additional Information: First Published on May 26, 2015 (online)
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: 10.1074/jbc.M115.646034
Depositing User: Matthew Conner
Date Deposited: 26 Jun 2015 13:11
Last Modified: 20 Aug 2015 11:14
URI: http://shura.shu.ac.uk/id/eprint/10595

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