Article tools
Author information
Published in Volume 102, Issue 1 (July 1,1998)
J. Clin. Invest. 102(1): 57-66 (1998). doi:10.1172/JCI2605.
Copyright © 1998, The American Society for Clinical Investigation.

Research Article

An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex.

S M Mulders, D G Bichet, J P Rijss, E J Kamsteeg, M F Arthus, M Lonergan, M Fujiwara, K Morgan, R Leijendekker, P van der Sluijs, C H van Os and P M Deen

Department Of Cell Physiology, University of Nijmegen, 6500 HB Nijmegen, The Netherlands.

Published July 1, 1998

Mutations in the aquaporin-2 (AQP2) water channel gene cause autosomal recessive nephrogenic diabetes insipidus (NDI). Here we report the first patient with an autosomal dominant form of NDI, which is caused by a G866A transition in the AQP2 gene of one allele, resulting in a E258K substitution in the C-tail of AQP2. To define the molecular cause of NDI in this patient, AQP2-E258K was studied in Xenopus oocytes. In contrast to wild-type AQP2, AQP2-E258K conferred a small increase in water permeability, caused by a reduced expression at the plasma membrane. Coexpression of wild-type AQP2 with AQP2-E258K, but not with an AQP2 mutant in recessive NDI (AQP2-R187C), revealed a dominant-negative effect on the water permeability conferred by wild-type AQP2. The physiologically important phosphorylation of S256 by protein kinase A was not affected by the E258K mutation. Immunoblot and microscopic analyses revealed that AQP2-E258K was, in contrast to AQP2 mutants in recessive NDI, not retarded in the endoplasmic reticulum, but retained in the Golgi compartment. Since AQPs are thought to tetramerize, the retention of AQP2-E258K together with wild-type AQP2 in mixed tetramers in the Golgi compartment is a likely explanation for the dominant inheritance of NDI in this patient.

This article Copyright © 1998, The American Society for Clinical Investigation.

Articles that cite
this article:

Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus
Erik-Jan Kamsteeg, Monique Stoffels, Grazia Tamma, Irene B.M. Konings, Peter M.T. Deen
Hum Mutat [CrossRef]

Aquaporins: a promising target for drug development
Kandiah Jeyaseelan, Sugunavathi Sepramaniam, Arunmozhiarasi Armugam, E Marelyn Wintour
eott 10(6):889. [CrossRef]

Urine concentration and avian aquaporin water channels
Hiroko Nishimura
Pflugers Arch 456(4):755. [CrossRef]


Yasumasa Iwasaki, Joseph Majzoub
CURR OPIN ENDOCRINOL DIABETES 6(2):112. [CrossRef]

From structure to disease: the evolving tale of aquaporin biology
Landon S. King, David Kozono, Peter Agre
Nat Rev Mol Cell Biol 5(9):687. [CrossRef]

Diversity of nephrogenic diabetes insipidus mutations and importance of early recognition and treatment
Daniel G. Bichet, T. Mary Fujiwara
Clin Exp Nephrol 2(4):253. [CrossRef]

Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine
David Kozono, Masato Yasui, Landon S. King, Peter Agre
J Clin Invest 109(11):1395. [CrossRef]

Missorting of the Aquaporin-2 mutant E258K to multivesicular bodies/lysosomes in dominant NDI is associated with its monoubiquitination and increased phosphorylation by PKC but is due to the loss of E258
Erik-Jan Kamsteeg, Paul J. M. Savelkoul, Giel Hendriks, Irene B. M. Konings, Nicole M. I. Nivillac, Anne Karine Lagendijk, Peter Sluijs, Peter M. T. Deen
Pflugers Arch 455(6):1041. [CrossRef]

Pharmacological Chaperones in Nephrogenic Diabetes Insipidus
Joris H Robben, Peter M T Deen
21(3):157. [CrossRef]

Molecular Mechanisms and Drug Development in Aquaporin Water Channel Diseases: Molecular Mechanism of Water Channel Aquaporin-2 Trafficking
Yumi Noda, Sei Sasaki
J Pharmacol Sci 96(3):249. [CrossRef]

Aquaporin Water Channels in the Kidney
Kuniaki Takata, Toshiyuki Matsuzaki, Yuki Tajika, Abdushukur Ablimit, Takeshi Suzuki, Takeo Aoki, Haruo Hagiwara
Acta Histochem Cytochem 38(3):199. [CrossRef]

Genetic variation in human aquaporins and effects on phenotypes of water homeostasis
Marco D. Sorani, Geoffrey T. Manley, Kathleen M. Giacomini
Hum Mutat 29(9):1108. [CrossRef]

Identification of two novel aquaporin-2 mutations in a Thai girl with congenital nephrogenic diabetes insipidus
Taninee Sahakitrungruang, Suttipong Wacharasindhu, Thivaratana Sinthuwiwat, Vichit Supornsilchai, Kanya Suphapeetiporn, Vorasuk Shotelersuk
ENDO 33(2):210. [CrossRef]

Molecular analyses of the vasopressin type 2 receptor and aquaporin-2 genes in Brazilian kindreds with nephrogenic diabetes insipidus
Juliane L. Rocha, Eitan Friedman, Wolfanga Boson, Ayrton Moreira, Bonald Figueiredo, Bernardo Liberman, Luiz De lacerda, Romulo Sandrini, Hans Graf, Sonia Martins
Hum Mutat 14(3):233. [CrossRef]

Protective Effects of Glycyrrhizin on Gentamicin-Induced Acute Renal Failure in Rats
Eun-Jin Sohn, Dae-Gill Kang, Ho-Sub Lee
Pharmacol Toxicol 93(3):116. [CrossRef]

QUALITY CONTROL AND PROTEIN FOLDING IN THE SECRETORY PATHWAY
E. Sergio Trombetta, Armando J. Parodi
annu rev cell dev biol 19(1):649. [CrossRef]

MODULATION OF VASOPRESSIN-ELICITED WATER TRANSPORT BY TRAFFICKING OF AQUAPORIN2-CONTAINING VESICLES1
Donald T. Ward, Timothy G. Hammond, H. William Harris
Annu Rev Physiol 61(1):683. [CrossRef]

NEPHROGENIC DIABETES INSIPIDUS
Jean-Pierre Morello, Daniel G Bichet
Annu Rev Physiol 63(1):607. [CrossRef]

Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations
Tomoki Asai, Michio Kuwahara, Hidetake Kurihara, Tatsuo Sakai, Yoshio Terada, Fumiaki Marumo, Sei Sasaki
Kidney Int 64(1):2. [CrossRef]

Pathophysiological roles of arginine vasopressin and aquaporin-2 in impaired water excretion
San-e Ishikawa, Robert W. Schrier
Clin Endocrinol (Oxf) 58(1):1. [CrossRef]

THE AQUAPORIN-2 WATER CHANNEL IN AUTOSOMAL DOMINANT PRIMARY NOCTURNAL ENURESIS
PETER M. T. Deen, NIKLAS Dahl, MICHAEL J. Caplan
Journal of Urology [CrossRef]

EDITORIAL: ARE AQUAPORIN WATER CHANNELS THE ???HOLY GRAIL??? OF PRIMARY NOCTURNAL ENURESIS?
Ira D. Davis, Katherine Macrae dell
Journal of Urology [CrossRef]

Naturally Occurring Mutations in the Thyroglobulin Gene
Jussara Vono-toniolo, Carina M. Rivolta, Hector M. Targovnik, Geraldo Medeiros-neto, Peter Kopp
15(9):1021. [CrossRef]

CELLULAR AND MOLECULAR BIOLOGY OF THE AQUAPORIN WATER CHANNELS
Mario Borgnia, Søren Nielsen, Andreas Engel, Peter Agre
Annu Rev Biochem 68(1):425. [CrossRef]

Molecular basis and clinical features of nephrogenic diabetes insipidus
Angela Schulz, Holger Römpler, Doreen Mitschke, Doreen Thor, Nicole Schliebe, Thomas Hermsdorf, Rainer Strotmann, Katrin Sangkuhl, Torsten Schöneberg
Expert Rev Endocrinol Metab 1(6):727. [CrossRef]

Nephrogenic diabetes insipidus
Peter M.T. Deen, Nannette Marr, Erik-Jan Kamsteeg, Bas W.M. Van balkom
9(6):591. [CrossRef]

Novel Vasopressin Type 2 (AVPR2) Gene Mutations in Brazilian Nephrogenic Diabetes Insipidus Patients
W.L. Boson, T. Della Manna, D. Damiani, D.M. Miranda, M.R. Gadelha, B. Liberman, H. Correa, M.A. Romano-silva, E. Friedman, F.F. Silva
Genet Test 10(3):157. [CrossRef]

Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption
Michelle Boone, Peter M. T. Deen
Pflugers Arch 456(6):1005. [CrossRef]

Regulation and dysregulation of aquaporins in water balance disorders
S. Nielsen, T.-H. Kwon, J. Frøkiær, P. Agre
J Intern Med 261(1):53. [CrossRef]

Dominant and Recessive Distal Renal Tubular Acidosis Mutations of Kidney Anion Exchanger 1 Induce Distinct Trafficking Defects in MDCK Cells
Emmanuelle Cordat, Saranya Kittanakom, Pa-thai Yenchitsomanus, Jing Li, Kai Du, Gergely L. Lukacs, Reinhart A. F. Reithmeier
7(2):117. [CrossRef]

Characterization of V71M mutation in the aquaporin-2 gene causing nephrogenic diabetes insipidus
N. Bougacha-elleuch, M. Lassoued, N. Miled, S. Zouari, H. Ayadi
J Genet 87(3):279. [CrossRef]