Rapid aquaporin translocation regulates cellular water flow:the mechanism of hypotonicity-induced sub-cellular localization of the aquaporin 1 water channel


The control of cellular water flow is mediated by the aquaporin (AQP) family of membrane proteins. The family's structural features and the mechanism of selective water passage through the AQP pore are established, but there remains a gap in our knowledge of how water transport is regulated. Two broad possibilities exist. One is controlling the passage of water through the AQP pore, but this has only been observed as a phenomenon in some plant and microbial AQPs. An alternative is controlling the number of AQPs in the cell membrane. Here we describe a novel pathway in mammalian cells whereby a hypotonic stimulus directly induces intracellular calcium elevations, through transient receptor potential channels, that trigger AQP1 translocation. This translocation, which has a direct role in cell volume regulation, occurs within 30s and is dependent on calmodulin activation and phosphorylation of AQP1 at two threonine residues by protein kinase C. This direct mechanism provides a rationale for the changes in water transport that are required in response to constantly-changing local cellular water availability. Moreover, since calcium is a pluripotent and ubiquitous second messenger in biological systems, the discovery of its role in the regulation of AQP translocation has ramifications for diverse physiological and pathophysiological processes, as well as providing an explanation for the rapid regulation of water flow that is necessary for cell homeostasis.

Publication DOI: https://doi.org/10.1074/jbc.M111.329219
Divisions: College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Aston Pharmacy School
Additional Information: Author Choice Articles - Creative Commons Attribution Non-Commercial License
Uncontrolled Keywords: aquaporins,calcium channels,cellular regulation,membrane trafficking,phosphorylation,water channel,homeostasis,hypotonicity,Biochemistry,Cell Biology,Molecular Biology
Publication ISSN: 1083-351X
Last Modified: 19 Jul 2024 07:02
Date Deposited: 11 Jul 2012 10:27
Full Text Link: http://www.jbc. ... nt/287/14/11516
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2012-03-30
Published Online Date: 2012-02-09
Authors: Conner, Matthew T.
Conner, Alex C.
Bland, Charlotte E.
Taylor, Luke H.J.
Brown, James (ORCID Profile 0000-0002-3504-7373)
Parri, H. Rheinallt (ORCID Profile 0000-0002-1412-2688)
Bill, Roslyn M. (ORCID Profile 0000-0003-1331-0852)



Version: Published Version

License: Creative Commons Attribution Non-commercial

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