Next Article in Journal
Different Susceptibilities between Apoe- and Ldlr-Deficient Mice to Inflammation-Associated Colorectal Carcinogenesis
Next Article in Special Issue
Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria nigriventer Spider Venom
Previous Article in Journal
The Expression and Clinical Outcome of pCHK2-Thr68 and pCDC25C-Ser216 in Breast Cancer
Previous Article in Special Issue
Involvement of JNK/NFκB Signaling Pathways in the Lipopolysaccharide-Induced Modulation of Aquaglyceroporin Expression in 3T3-L1 Cells Differentiated into Adipocytes
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(11), 1804; doi:10.3390/ijms17111804

AQP2 Plasma Membrane Diffusion Is Altered by the Degree of AQP2-S256 Phosphorylation

1
Department of Clinical Medicine, Aarhus University, DK-8000 Aarhus C, Denmark
2
The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
3
Department of Interdisciplinary Nanoscience Center, Aarhus University, DK-8000 Aarhus C, Denmark
Current address: Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Current address: Janelia Research Campus, Ashburn, VA 20147, USA.
*
Author to whom correspondence should be addressed.
Academic Editor: Kenichi Ishibashi
Received: 19 July 2016 / Revised: 15 September 2016 / Accepted: 22 September 2016 / Published: 28 October 2016
(This article belongs to the Special Issue Aquaporin)
View Full-Text   |   Download PDF [2749 KB, uploaded 28 October 2016]   |  

Abstract

Fine tuning of urine concentration occurs in the renal collecting duct in response to circulating levels of arginine vasopressin (AVP). AVP stimulates intracellular cAMP production, which mediates exocytosis of sub-apical vesicles containing the water channel aquaporin-2 (AQP2). Protein Kinase A (PKA) phosphorylates AQP2 on serine-256 (S256), which triggers plasma membrane accumulation of AQP2. This mediates insertion of AQP2 into the apical plasma membrane, increasing water permeability of the collecting duct. AQP2 is a homo-tetramer. When S256 on all four monomers is changed to the phosphomimic aspartic acid (S256D), AQP2-S256D localizes to the plasma membrane and internalization is decreased. In contrast, when S256 is mutated to alanine (S256A) to mimic non-phosphorylated AQP2, AQP2-S256A localizes to intracellular vesicles as well as the plasma membrane, with increased internalization from the plasma membrane. S256 phosphorylation is not necessary for exocytosis and dephosphorylation is not necessary for endocytosis, however, the degree of S256 phosphorylation is hypothesized to regulate the kinetics of AQP2 endocytosis and thus, retention time in the plasma membrane. Using k-space Image Correlation Spectroscopy (kICS), we determined how the number of phosphorylated to non-phosphorylated S256 monomers in the AQP2 tetramer affects diffusion speed of AQP2 in the plasma membrane. When all four monomers mimicked constitutive phosphorylation (AQP2-S256D), diffusion was faster than when all four were non-phosphorylated (AQP2-S256A). AQP2-WT diffused at a speed similar to that of AQP2-S256D. When an average of two or three monomers in the tetramer were constitutively phosphorylated, the average diffusion coefficients were not significantly different to that of AQP2-S256D. However, when only one monomer was phosphorylated, diffusion was slower and similar to AQP2-S256A. Thus, AQP2 with two to four phosphorylated monomers has faster plasma membrane kinetics, than the tetramer which contains just one or no phosphorylated monomers. This difference in diffusion rate may reflect behavior of AQP2 tetramers destined for either plasma membrane retention or endocytosis. View Full-Text
Keywords: diffusion coefficients; kICS: k-space Image Correlation Spectroscopy; MDCK; AQP2; kidney; urine; phosphorylation diffusion coefficients; kICS: k-space Image Correlation Spectroscopy; MDCK; AQP2; kidney; urine; phosphorylation
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary materials

  • Supplementary File 1:

    Supplementary (PDF, 600 KB)

  • Externally hosted supplementary file 1
    Doi: NA
    Link: http://NA
    Description: Table S1 and Table S2

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Arnspang, E.C.; Login, F.H.; Koffman, J.S.; Sengupta, P.; Nejsum, L.N. AQP2 Plasma Membrane Diffusion Is Altered by the Degree of AQP2-S256 Phosphorylation. Int. J. Mol. Sci. 2016, 17, 1804.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top