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Plasma Membrane Abundance of Human Aquaporin 5 Is Dynamically Regulated by Multiple Pathways.

Kitchen, Philip; Öberg, Fredrik; Sjöhamn, Jennie; Hedfalk, Kristina; Bill, Roslyn M; Conner, Alex C; Conner, Matthew T and Horsefield, Susanna LU (2015) In PLoS ONE 10(11).
Abstract
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... (More)
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. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
10
issue
11
publisher
Public Library of Science
external identifiers
  • pmid:26569106
  • wos:000365070700122
  • scopus:84957108681
ISSN
1932-6203
DOI
10.1371/journal.pone.0143027
language
English
LU publication?
yes
id
9d9f183b-36db-443e-928e-6893d98ea7cc (old id 8235460)
date added to LUP
2015-12-07 12:41:40
date last changed
2017-11-19 03:54:11
@article{9d9f183b-36db-443e-928e-6893d98ea7cc,
  abstract     = {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.},
  articleno    = {e0143027},
  author       = {Kitchen, Philip and Öberg, Fredrik and Sjöhamn, Jennie and Hedfalk, Kristina and Bill, Roslyn M and Conner, Alex C and Conner, Matthew T and Horsefield, Susanna},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Plasma Membrane Abundance of Human Aquaporin 5 Is Dynamically Regulated by Multiple Pathways.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0143027},
  volume       = {10},
  year         = {2015},
}