title: The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system.
abstract: 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.
authors.affiliation: Institut de Recherches Interdisciplinaires en Biologie Humaine et Moléculaire, Brussels, Belgium.
authors.forename: Eileen
authors.initials: E
authors.lastname: Pernot
authors.forename: Sara
authors.initials: S
authors.lastname: Terryn
authors.forename: Siew Chiat
authors.initials: SC
authors.lastname: Cheong
authors.forename: Nicolas
authors.initials: N
authors.lastname: Markadieu
authors.forename: Sylvie
authors.initials: S
authors.lastname: Janas
authors.forename: Marianne
authors.initials: M
authors.lastname: Blockmans
authors.forename: Monique
authors.initials: M
authors.lastname: Jacoby
authors.forename: Valérie
authors.initials: V
authors.lastname: Pouillon
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gayral
authors.forename: Bernard C
authors.initials: BC
authors.lastname: Rossier
authors.forename: Renaud
authors.initials: R
authors.lastname: Beauwens
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.forename: Stéphane
authors.initials: S
authors.lastname: Schurmans
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014667:Vasopressins / Q000378:metabolism*; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D051399:Aquaporin 2; D014867:Water; D014667:Vasopressins; C531212:Pps protein, mouse; D010744:Phosphoric Monoester Hydrolases