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Plasma membrane abundance of human aquaporin 5 is dynamically regulated by multiple pathways
Kitchen, P Öberg, F Sjöhamn, J Hedfalk, K Bill, RM Törnroth-Horsefield, S Conner, Matthew T. Conner, Alex C.
Kitchen, P
Öberg, F
Sjöhamn, J
Hedfalk, K
Bill, RM
Törnroth-Horsefield, S
Conner, Matthew T.
Conner, Alex C.
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2015-11-16
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Abstract
© 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. 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.
Citation
Kitchen P., Öberg F., Sjöhamn J., Hedfalk K., Bill R. M., Conner A. C., et al. (2015) Plasma membrane abundance of human Aquaporin 5 Is dynamically regulated by multiple pathways. PLoS ONE 10(11): e0143027. doi:10.1371/journal.pone.0143027.
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PubMed ID
26569106
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Journal article
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en
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1932-6203
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This work was supported by the Swedish Research Council (www.vr.se) grants 2009-360 and 2010-5208 (to STH), European Commission Framework Programme 7 (http://ec.europa.eu/research/fp7/index_en.cfm) Grant 201924 EDICT (to RMB) and by the Engineering and Physical Sciences Research Council (https://www.epsrc.ac.uk) through the Molecular Organisation and Assembly in Cells Doctoral Training Centre, University of Warwick, grant number EP/F500378/1 (PK).
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Licence for published version: Creative Commons Attribution 4.0 International