Identification and Molecular Mechanisms of the Rapid Tonicity-induced Relocalization of the Aquaporin 4 Channel

Philip Kitchen, Rebecca E Day, Luke H J Taylor, Mootaz M Salman, Roslyn M Bill, Matthew T Conner, Alex C Conner

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42 Citations (Scopus)
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The aquaporin family of integral membrane proteins is composed 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 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 edema.

Original languageEnglish
Pages (from-to)16873-16881
Number of pages9
JournalJournal of Biological Chemistry
Issue number27
Publication statusPublished - 3 Jul 2015


  • Amino Acid Motifs
  • Animals
  • Aquaporin 4
  • Astrocytes
  • Brain Edema
  • Calcium
  • Calmodulin
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases
  • HEK293 Cells
  • Humans
  • Osmotic Pressure
  • Phosphorylation
  • Protein Transport
  • Rats
  • Journal Article
  • Research Support, Non-U.S. Gov't


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