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Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9.
J Biol Chem. 2008 Feb 01; 283(5):2986-96.JB

Abstract

Water and solute transport across the plasma membrane of cells is a crucial biological function that is mediated mainly by aquaporins and aquaglyceroporins. The regulation of these membrane proteins is still incompletely understood. Using the male reproductive tract as a model system in which water and glycerol transport are critical for the establishment of fertility, we now report a novel pathway for the regulation of aquaporin 9 (AQP9) permeability. AQP9 is the major aquaglyceroporin of the epididymis, liver, and peripheral leukocytes, and its COOH-terminal portion contains a putative PDZ binding motif (SVIM). Here we show that NHERF1, cystic fibrosis transmembrane conductance regulator (CFTR), and AQP9 co-localize in the apical membrane of principal cells of the epididymis and the vas deferens, and that both NHERF1 and CFTR co-immunoprecipitate with AQP9. Overlay assays revealed that AQP9 binds to both the PDZ1 and PDZ2 domains of NHERF1, with an apparently higher affinity for PDZ1 versus PDZ2. Pull-down assays showed that the AQP9 COOH-terminal SVIM motif is essential for interaction with NHERF1. Functional assays on isolated tubules perfused in vitro showed a high permeability of the apical membrane to glycerol, which is inhibited by the AQP9 inhibitor, phloretin, and is markedly activated by cAMP. The CFTR inhibitors DPC, GlyH-101 and CFTRinh-172 all significantly reduced the cAMP-activated glycerol-induced cell swelling. We propose that CFTR is an important regulator of AQP9 and that the interaction between AQP9, NHERF1, and CFTR may facilitate the activation of AQP9 by cAMP.

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Authors+Show Affiliations

Pietrement C
Center for Systems Biology, Program in Membrane Biology/Nephrology Division, Simches Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.
Da Silva N
No affiliation info available
Silberstein C
No affiliation info available
James M
No affiliation info available
Marsolais M
No affiliation info available
Van Hoek A
No affiliation info available
Brown D
No affiliation info available
Pastor-Soler N
No affiliation info available
Ameen N
No affiliation info available
Laprade R
No affiliation info available
Ramesh V
No affiliation info available
Breton S
No affiliation info available

MeSH

Amino Acid SequenceAnimalsAquaporinsBinding SitesCyclic AMPCystic Fibrosis Transmembrane Conductance RegulatorEpididymisFertilityIn Vitro TechniquesMaleMolecular Sequence DataPhosphoproteinsProtein Structure, TertiaryRatsRats, Sprague-DawleyRecombinant ProteinsSodium-Hydrogen ExchangersVas Deferens

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18055461

Citation

Pietrement, Christine, et al. "Role of NHERF1, Cystic Fibrosis Transmembrane Conductance Regulator, and cAMP in the Regulation of Aquaporin 9." The Journal of Biological Chemistry, vol. 283, no. 5, 2008, pp. 2986-96.
Pietrement C, Da Silva N, Silberstein C, et al. Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9. J Biol Chem. 2008;283(5):2986-96.
Pietrement, C., Da Silva, N., Silberstein, C., James, M., Marsolais, M., Van Hoek, A., Brown, D., Pastor-Soler, N., Ameen, N., Laprade, R., Ramesh, V., & Breton, S. (2008). Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9. The Journal of Biological Chemistry, 283(5), 2986-96.
Pietrement C, et al. Role of NHERF1, Cystic Fibrosis Transmembrane Conductance Regulator, and cAMP in the Regulation of Aquaporin 9. J Biol Chem. 2008 Feb 1;283(5):2986-96. PubMed PMID: 18055461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of NHERF1, cystic fibrosis transmembrane conductance regulator, and cAMP in the regulation of aquaporin 9. AU - Pietrement,Christine, AU - Da Silva,Nicolas, AU - Silberstein,Claudia, AU - James,Marianne, AU - Marsolais,Mireille, AU - Van Hoek,Alfred, AU - Brown,Dennis, AU - Pastor-Soler,Nuria, AU - Ameen,Nadia, AU - Laprade,Raynald, AU - Ramesh,Vijaya, AU - Breton,Sylvie, Y1 - 2007/11/30/ PY - 2007/12/7/pubmed PY - 2008/4/3/medline PY - 2007/12/7/entrez SP - 2986 EP - 96 JF - The Journal of biological chemistry JO - J Biol Chem VL - 283 IS - 5 N2 - Water and solute transport across the plasma membrane of cells is a crucial biological function that is mediated mainly by aquaporins and aquaglyceroporins. The regulation of these membrane proteins is still incompletely understood. Using the male reproductive tract as a model system in which water and glycerol transport are critical for the establishment of fertility, we now report a novel pathway for the regulation of aquaporin 9 (AQP9) permeability. AQP9 is the major aquaglyceroporin of the epididymis, liver, and peripheral leukocytes, and its COOH-terminal portion contains a putative PDZ binding motif (SVIM). Here we show that NHERF1, cystic fibrosis transmembrane conductance regulator (CFTR), and AQP9 co-localize in the apical membrane of principal cells of the epididymis and the vas deferens, and that both NHERF1 and CFTR co-immunoprecipitate with AQP9. Overlay assays revealed that AQP9 binds to both the PDZ1 and PDZ2 domains of NHERF1, with an apparently higher affinity for PDZ1 versus PDZ2. Pull-down assays showed that the AQP9 COOH-terminal SVIM motif is essential for interaction with NHERF1. Functional assays on isolated tubules perfused in vitro showed a high permeability of the apical membrane to glycerol, which is inhibited by the AQP9 inhibitor, phloretin, and is markedly activated by cAMP. The CFTR inhibitors DPC, GlyH-101 and CFTRinh-172 all significantly reduced the cAMP-activated glycerol-induced cell swelling. We propose that CFTR is an important regulator of AQP9 and that the interaction between AQP9, NHERF1, and CFTR may facilitate the activation of AQP9 by cAMP. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/18055461/Role_of_NHERF1_cystic_fibrosis_transmembrane_conductance_regulator_and_cAMP_in_the_regulation_of_aquaporin_9_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)55546-4 DB - PRIME DP - Unbound Medicine ER -