Plasma membrane abundance of human aquaporin 5 is dynamically regulated by multiple pathways


Aquaporin membrane protein channels mediate cellular water flow. Human aquaporin 5 (AQP5) is highly expressed in the respiratory system and secretory glands where it facilitates the osmotically-driven generation of pulmonary secretions, saliva, sweat and tears. Dysfunctional trafficking of AQP5 has been implicated in several human disease states, including Sjögren’s syndrome, bronchitis and cystic fibrosis. In order to investigate how the plasma membrane expression levels of AQP5 are regulated, we studied real-time translocation of GFP-tagged AQP5 in HEK293 cells. We show that AQP5 plasma membrane abundance in transfected HEK293 cells is rapidly and reversibly regulated by at least three independent mechanisms involving phosphorylation at Ser156, protein kinase A activity and extracellular tonicity. The crystal structure of a Ser156 phosphomimetic mutant indicates that its involvement in regulating AQP5 membrane abundance is not mediated by a conformational change of the carboxy-terminus. We suggest that together these pathways regulate cellular water flow.

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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: © 2015 Kitchen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Swedish Research Council ( (2009-360; 2010-5208); EC FP7 ( (201924 EDICT); and EPSRC ( (EP/F500378/1). Data: Coordinates and structure factors are available from the Protein Data Bank, accession codes 5DYE and 5C5X. All other relevant data are within the paper.
Uncontrolled Keywords: General Agricultural and Biological Sciences,General Biochemistry,Genetics and Molecular Biology,General Medicine
Publication ISSN: 1932-6203
Last Modified: 27 Jun 2024 08:43
Date Deposited: 03 Dec 2015 16:30
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://journals ... al.pone.0143027 (Publisher URL)
PURE Output Type: Article
Published Date: 2015-11-16
Accepted Date: 2015-10-29
Submitted Date: 2015-07-01
Authors: Kitchen, Philip (ORCID Profile 0000-0002-1558-4673)
Öberg, Fredrik
Sjöhamn, Jennie
Hedfalk, Kristina
Bill, Roslyn M. (ORCID Profile 0000-0003-1331-0852)
Conner, Alex C.
Conner, Matthew T.
Törnroth-Horsefield, Susanna



Version: Published Version

License: Creative Commons Attribution

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