2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by ALBERTAZZI, E. Articles by CHINI, B. Search for Related Content PubMed PubMed Citation Articles by ALBERTAZZI, E. Articles by CHINI, B.

Nephrogenic Diabetes Insipidus

Functional Analysis of New AVPR2Mutations Identified in Italian Families

ELENA ALBERTAZZI^*, DEBORAH ZANCHETTA^*, PASCALINE BARBIER^*, SARA FARANDA, ANNALISA FRATTINI, PAOLO VEZZONI, MIRELLA PROCACCIO, ALBERTO BETTINELLI, FRANCESCA GUZZI^§, MARCO PARENTI^§ and BICE CHINI^*

^* Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology Center, Milan, Italy.^,a
Consiglio Nazionale delle Ricerche Institute of Advanced Biomedical Technologies, Milan, Italy.
II Paediatric Clinic, Milan, Italy.
^§ Department of Pharmacology, University of Milan, Milan, Italy.

Correspondence to Dr. Bice Chini, Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology Center, via Vanvitelli 32, 20129 Milan, Italy. Phone: +39 02 70146271; Fax: +39 02 7490574; E-mail: B.Chini{at}csfic.mi.cnr.it

Abstract. The aim of this study was to identify loss-of-function mutations of the V2 vasopressin receptor gene (AVPR2) in Italian patients affected by X-linked nephrogenic diabetes insipidus (NDI). Mutations were found in 15 of the 18 unrelated families investigated: nine of these mutations were previously unknown, including two affecting residues located in regions known to be important for determining the pharmacologic properties of the receptor, which were therefore functionally investigated. The first (A84D) involves a residue located near an aspartic acid (D85) that is highly conserved in all G protein-coupled receptors and that is believed to play a role in the process of their isomerization into functionally active and inactive states. The present study indicates that this mutation not only affects receptor folding in such a way as to lead to its retention inside the intracellular compartments but, as expected, also has profound effects on its binding and coupling properties. The second was a mutation of a tryptophan located at the beginning of the first extracellular loop (W99R) that greatly impaired the binding properties of the receptor and had a minor effect on its intracellular routing. Molecular analysis of the first extracellular loop bearing this mutation suggests that this residue plays a fundamental role in stabilizing the peptide/receptor interactions responsible for the high-affinity binding of agonists to the V2 receptor.

This article has been cited by other articles:

				J. H. Robben, N. V. A. M. Knoers, and P. M. T. Deen Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol, August 1, 2006; 291(2): F257 - F270. [Abstract] [Full Text] [PDF]

				M.-F. ARTHUS, M. LONERGAN, M. J. CRUMLEY, A. K. NAUMOVA, D. MORIN, L. A. DE MARCO, B. S. KAPLAN, G. L. ROBERTSON, S. SASAKI, K. MORGAN, et al. Report of 33 Novel AVPR2 Mutations and Analysis of 117 Families with X-Linked Nephrogenic Diabetes Insipidus J. Am. Soc. Nephrol., June 1, 2000; 11(6): 1044 - 1054. [Abstract] [Full Text]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673