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

VALENTI, Giovanna, KITCHEN, Philip, ÖBERG, Fredrik, SJÖHAMN, Jennie, HEDFALK, Kristina, BILL, Roslyn M., CONNER, Alex C., CONNER, Matthew T. and TÖRNROTH-HORSEFIELD, Susanna (2015). Plasma membrane abundance of human aquaporin 5 is dynamically regulated by multiple pathways. PLOS ONE, 10 (11), e0143027.

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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.

Item Type: Article
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: 10.1371/journal.pone.0143027
Depositing User: Ann Betterton
Date Deposited: 29 Sep 2016 13:15
Last Modified: 19 Oct 2016 23:05

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