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EMBO J
1999 May 04;189:2394-400. doi: 10.1093/emboj/18.9.2394.
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An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus.
Kamsteeg EJ
,
Wormhoudt TA
,
Rijss JP
,
van Os CH
,
Deen PM
.
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Autosomal recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, are caused by mutations in the aquaporin-2 (AQP2) gene. Missense AQP2 proteins in recessive NDI have been shown to be retarded in the endoplasmic reticulum, whereas AQP2-E258K, an AQP2 mutant in dominant NDI, was retained in the Golgi complex. In this study, we identified the molecular mechanisms underlying recessive and dominant NDI. Sucrose gradient centrifugation of rat and human kidney proteins and subsequent immunoblotting revealed that AQP2 forms homotetramers. When expressed in oocytes, wild-type AQP2 and AQP2-E258K also formed homotetramers, whereas AQP2-R187C, a mutant in recessive NDI, was expressed as a monomer. Upon co-injection, AQP2-E258K, but not AQP2-R187C, was able to heterotetramerize with wild-type AQP2. Since an AQP monomer is the functional unit and AQP2-E258K is a functional but misrouted water channel, heterotetramerization of AQP2-E258K with wild-type AQP2 and inhibition of further routing of this complex to the plasma membrane is the cause of dominant NDI. This case of NDI is the first example of a dominant disease in which the 'loss-of-function' phenotype is caused by an impaired routing rather than impaired function of the wild-type protein.
Cosma,
Mutations in the extracellular domain cause RET loss of function by a dominant negative mechanism.
1998, Pubmed
Cosma,
Mutations in the extracellular domain cause RET loss of function by a dominant negative mechanism.
1998,
Pubmed
Deen,
Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine.
1994,
Pubmed
,
Xenbase
Deen,
Urinary content of aquaporin 1 and 2 in nephrogenic diabetes insipidus.
1996,
Pubmed
,
Xenbase
Deen,
Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing.
1995,
Pubmed
,
Xenbase
Ecelbarger,
Aquaporin-3 water channel localization and regulation in rat kidney.
1995,
Pubmed
Glowatzki,
Subunit-dependent assembly of inward-rectifier K+ channels.
1995,
Pubmed
,
Xenbase
Hurtley,
Protein oligomerization in the endoplasmic reticulum.
1989,
Pubmed
Jung,
Molecular structure of the water channel through aquaporin CHIP. The hourglass model.
1994,
Pubmed
,
Xenbase
Katsura,
Constitutive and regulated membrane expression of aquaporin 1 and aquaporin 2 water channels in stably transfected LLC-PK1 epithelial cells.
1995,
Pubmed
King,
Pathophysiology of the aquaporin water channels.
1996,
Pubmed
Koiwai,
Crigler-Najjar syndrome type II is inherited both as a dominant and as a recessive trait.
1996,
Pubmed
König,
Characterisation of the major intrinsic protein (MIP) from bovine lens fibre membranes by electron microscopy and hydrodynamics.
1997,
Pubmed
Kopito,
ER quality control: the cytoplasmic connection.
1997,
Pubmed
Kreis,
Microinjected antibodies against the cytoplasmic domain of vesicular stomatitis virus glycoprotein block its transport to the cell surface.
1986,
Pubmed
Le Maire,
The use of high-performance liquid chromatography for the determination of size and molecular weight of proteins: a caution and a list of membrane proteins suitable as standards.
1986,
Pubmed
Li,
A fibrillar collagen gene, Col11a1, is essential for skeletal morphogenesis.
1995,
Pubmed
Marples,
Redistribution of aquaporin-2 water channels induced by vasopressin in rat kidney inner medullary collecting duct.
1995,
Pubmed
Mulders,
New mutations in the AQP2 gene in nephrogenic diabetes insipidus resulting in functional but misrouted water channels.
1997,
Pubmed
,
Xenbase
Mulders,
An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex.
1998,
Pubmed
,
Xenbase
Musil,
Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER.
1993,
Pubmed
,
Xenbase
Nielsen,
Renal aquaporins: key roles in water balance and water balance disorders.
1998,
Pubmed
Nielsen,
Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane.
1995,
Pubmed
Preston,
The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel.
1993,
Pubmed
,
Xenbase
Rose,
Regulation of protein export from the endoplasmic reticulum.
1988,
Pubmed
Rosenthal,
Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus.
1992,
Pubmed
Schnermann,
Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice.
1998,
Pubmed
Seppen,
A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II.
1996,
Pubmed
Shiels,
Mutations in the founder of the MIP gene family underlie cataract development in the mouse.
1996,
Pubmed
Smith,
Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins.
1991,
Pubmed
Tamarappoo,
Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones.
1998,
Pubmed
,
Xenbase
Tatu,
Folding and oligomerization of influenza hemagglutinin in the ER and the intermediate compartment.
1995,
Pubmed
Terris,
Distribution of aquaporin-4 water channel expression within rat kidney.
1995,
Pubmed
Tinker,
Regions responsible for the assembly of inwardly rectifying potassium channels.
1996,
Pubmed
,
Xenbase
van den Ouweland,
Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus.
1992,
Pubmed
van Hoek,
Functional unit of 30 kDa for proximal tubule water channels as revealed by radiation inactivation.
1991,
Pubmed
van Lieburg,
Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.
1994,
Pubmed
,
Xenbase
Verbavatz,
Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: a freeze-fracture study.
1993,
Pubmed
Verkarre,
Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.
1998,
Pubmed
Vikkula,
Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus.
1995,
Pubmed
Walz,
The three-dimensional structure of aquaporin-1.
1997,
Pubmed
,
Xenbase
Yamamoto,
Vasopressin increases AQP-CD water channel in apical membrane of collecting duct cells in Brattleboro rats.
1995,
Pubmed
