Pflügers Archiv - European Journal of Physiology

, Volume 462, Issue 6, pp 871–883 | Cite as

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

  • Eileen Pernot
  • Sara Terryn
  • Siew Chiat Cheong
  • Nicolas Markadieu
  • Sylvie Janas
  • Marianne Blockmans
  • Monique Jacoby
  • Valérie Pouillon
  • Stéphanie Gayral
  • Bernard C. Rossier
  • Renaud Beauwens
  • Christophe Erneux
  • Olivier Devuyst
  • Stéphane Schurmans
Molecular and Genomic Physiology


Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting ducts.


Water transport Aquaporin Phosphoinositide metabolism 5-Phosphatase Collecting duct 



We thank Y. Maréchal (IRIBHM, IBMM), A. Ahrabi and H. Belge (Division of Nephrology, UCL) for discussions, C. Moreau (IRIBHM), H. Debaix, V. Beaujean and Y. Cnops (Division of Nephrology, UCL) for technical assistance, and D. Trono (Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland) for lentiviral reagents. This work was supported by the Fonds de la Recherche Scientifique-FNRS (FRS-FNRS)(to V.P., S.S., C.E. and O.D.), the Fonds pour la Formation à la Recherche dans l’Industrie et dans l’Agriculture (FRIA)(fellowships to E.P., M.B. and M.J.), the Fonds de la Recherche Scientifique Médicale (FRSM) (to S.S., C.E. and O.D.), the Fonds David et Alice Van Buuren (to M.J.), the Fondation Rose et Jean Hoguet (to E.P.), and a Concerted Research Action (05/10-328), The Chaire Spadel “Eau et Santé” at the UCL (O.D.), an Inter-University Attraction Pole (IUAP P6/05 to O.D.; IUAP P6/28 to C.E.), the NCCR Kidney CH program of the Swiss National Science Foundation and the EUNEFRON project of the European Community (FP7) to O.D.

Supplementary material

424_2011_1028_MOESM1_ESM.doc (35 kb)
Supplementary Table 1Primers sequences (DOC 35 kb)
424_2011_1028_MOESM2_ESM.doc (28 kb)
Supplementary Table 2Baseline parameters, renal function and water metabolism in Inpp5k transgenic mice (DOC 28 kb)
424_2011_1028_MOESM3_ESM.doc (28 kb)
Supplementary Information(DOC 28 kb)
424_2011_1028_MOESM4_ESM.doc (24 kb)
Supplementary Figure Legends(DOC 24.5 kb)
424_2011_1028_MOESM5_ESM.pdf (158 kb)
Supplementary Figure 1(PDF 158 kb)
424_2011_1028_MOESM6_ESM.pdf (79 kb)
Supplementary Figure 2(PDF 78.9 kb)
424_2011_1028_MOESM7_ESM.pdf (136 kb)
Supplementary Figure 3(PDF 136 kb)
424_2011_1028_MOESM8_ESM.pdf (58 kb)
Supplementary Figure 4(PDF 57.6 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Eileen Pernot
    • 1
    • 2
  • Sara Terryn
    • 3
  • Siew Chiat Cheong
    • 1
    • 2
  • Nicolas Markadieu
    • 4
  • Sylvie Janas
    • 3
  • Marianne Blockmans
    • 1
    • 2
  • Monique Jacoby
    • 1
    • 2
  • Valérie Pouillon
    • 1
    • 2
  • Stéphanie Gayral
    • 1
    • 2
  • Bernard C. Rossier
    • 5
  • Renaud Beauwens
    • 4
  • Christophe Erneux
    • 1
  • Olivier Devuyst
    • 3
    • 6
  • Stéphane Schurmans
    • 1
    • 2
    • 7
    • 8
  1. 1.Institut de Recherches Interdisciplinaires en Biologie Humaine et Moléculaire (IRIBHM)BrusselsBelgium
  2. 2.Institut de Biologie et de Médecine Moléculaires (IBMM)GosseliesBelgium
  3. 3.Division of NephrologyUniversité catholique de Louvain Medical SchoolBrusselsBelgium
  4. 4.Laboratoire de Physiologie Cellulaire et Moléculaire, Faculté de MédecineUniversité Libre de BruxellesBrusselsBelgium
  5. 5.Département de Pharmacologie et de ToxicologieUniversité de LausanneLausanneSwitzerland
  6. 6.Institute of Physiology, Zurich Centre for Integrative Human Physiology (ZIHP)University of ZurichZurichSwitzerland
  7. 7.Laboratoire de Génétique Fonctionnelle, GIGA-Research Centre/B34LiègeBelgium
  8. 8.Secteur de Biochimie Métabolique, Département des Sciences Fonctionnelles, Faculté de Médecine-VétérinaireUniversité de LiègeLiègeBelgium

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