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The aquaporin (AQP) transmembrane proteins facilitate the movement of water across the plasma membrane. In the lens, AQP0 is expressed in fiber cells and AQP1 in the epithelium. Recently, two individuals were identified with congenital polymorphic autosomal dominant cataract, due to a single nucleotide base deletion mutation in the lensAQP0. The deletion modified the reading frame resulting in the addition of a premature stop codon. In the present study, we examined the water permeability properties, trafficking and dominant negative effects as well as cytotoxicity due to the mutant AQP0 (Delta213-AQP0) protein. The membrane water permeability (P(w)) of Delta213-AQP0 expressing oocytes (14+/-1 microm/s) was significantly lower than those expressing WT-AQP0 (25+/-3 microm/s). P(w) of water injected control oocytes was 13+/-2 microm/s. Co-expression of WT-AQP0 with Delta213-AQP0 significantly lowered the P(w) (18+/-3 microm/s) compared to WT-AQP0. With or without the EGFP tag, WT-AQP0 protein localized in the plasma membranes of oocytes and cultured cells whereas Delta213-AQP0 was retained in the ER. Forster Resonance Energy Transfer (FRET) showed that WT-AQP0 partly localized with the co-expressed Delta213-AQP0. Co-localization studies suggest that the mutant AQP0 gained its dominant function by trapping the WT-AQP0 in the ER through hetero-oligomerization. Incubating the cells with chemical chaperones, namely, TMAO and DMSO, did not correct the folding/trafficking defects. Cell death in the Delta213-AQP0 expressing cells was due to necrosis caused by the accumulation of Delta213-AQP0 protein in the ER in cytotoxic proportions. The data show that replacement of the distal end of the 6th TM domain and the C-terminal domain of AQP0 due to the deletion mutation resulted in the impairment of cell membrane P(w), localization of the mutant protein in the ER without trafficking to the plasma membrane, and cytotoxicity due to the accumulation of the mutant protein. Cataracts in patients with this mutation might have resulted from the above mentioned consequences.
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18501347 ???displayArticle.pmcLink???PMC2504491 ???displayArticle.link???Exp Eye Res ???displayArticle.grants???[+]
Agre,
Membrane water transport and aquaporins: looking back.
2005, Pubmed
Agre,
Membrane water transport and aquaporins: looking back.
2005,
Pubmed Agre,
Aquaporin water channels--from atomic structure to clinical medicine.
2002,
Pubmed Al-Ghoul,
Lens structure in MIP-deficient mice.
2003,
Pubmed Ball,
Water permeability of C-terminally truncated aquaporin 0 (AQP0 1-243) observed in the aging human lens.
2003,
Pubmed
,
Xenbase Bassnett,
Lens organelle degradation.
2002,
Pubmed Bateman,
A new locus for autosomal dominant cataract on chromosome 12q13.
2000,
Pubmed Bates,
Model building by comparison at CASP3: using expert knowledge and computer automation.
1999,
Pubmed Bates,
Enhancement of protein modeling by human intervention in applying the automatic programs 3D-JIGSAW and 3D-PSSM.
2001,
Pubmed Berry,
Missense mutations in MIP underlie autosomal dominant 'polymorphic' and lamellar cataracts linked to 12q.
2000,
Pubmed Bonfoco,
Apoptosis and necrosis: two distinct events induced, respectively, by mild and intense insults with N-methyl-D-aspartate or nitric oxide/superoxide in cortical cell cultures.
1995,
Pubmed Buck,
A novel tripartite motif involved in aquaporin topogenesis, monomer folding and tetramerization.
2007,
Pubmed Bursch,
Cell death by apoptosis and its protective role against disease.
1992,
Pubmed Calamita,
Aquaporins: highways for cells to recycle water with the outside world.
2005,
Pubmed Carrell,
Alpha1-antitrypsin deficiency--a model for conformational diseases.
2002,
Pubmed Carrell,
Cell toxicity and conformational disease.
2005,
Pubmed Chandy,
Comparison of the water transporting properties of MIP and AQP1.
1997,
Pubmed
,
Xenbase Cheng,
Three-dimensional organization of a human water channel.
1997,
Pubmed Chepelinsky,
The ocular lens fiber membrane specific protein MIP/Aquaporin 0.
2003,
Pubmed Contreras-Moreira,
Domain fishing: a first step in protein comparative modelling.
2002,
Pubmed Crabbe,
Cataract as a conformational disease--the Maillard reaction, alpha-crystallin and chemotherapy.
1998,
Pubmed Das,
On the substrate specificity of alpha-crystallin as a molecular chaperone.
1995,
Pubmed Deen,
Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine.
1994,
Pubmed
,
Xenbase de Groot,
The dynamics and energetics of water permeation and proton exclusion in aquaporins.
2005,
Pubmed de Mattia,
A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L.
2004,
Pubmed
,
Xenbase Denning,
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive.
1992,
Pubmed
,
Xenbase Dovrat,
Effects of UV-A radiation on lens epithelial NaK-ATPase in organ culture.
1999,
Pubmed Duchesne,
Role of C-terminal domain and transmembrane helices 5 and 6 in function and quaternary structure of major intrinsic proteins: analysis of aquaporin/glycerol facilitator chimeric proteins.
2002,
Pubmed
,
Xenbase Francis,
Functional impairment of lens aquaporin in two families with dominantly inherited cataracts.
2000,
Pubmed
,
Xenbase Francis,
Congenital progressive polymorphic cataract caused by a mutation in the major intrinsic protein of the lens, MIP (AQP0).
2000,
Pubmed Fu,
Structure of a glycerol-conducting channel and the basis for its selectivity.
2000,
Pubmed Geyer,
Novel single-base deletional mutation in major intrinsic protein (MIP) in autosomal dominant cataract.
2006,
Pubmed Gonen,
Lipid-protein interactions in double-layered two-dimensional AQP0 crystals.
2005,
Pubmed Gorin,
The major intrinsic protein (MIP) of the bovine lens fiber membrane: characterization and structure based on cDNA cloning.
1984,
Pubmed Hamann,
Aquaporins in complex tissues: distribution of aquaporins 1-5 in human and rat eye.
1998,
Pubmed Harding,
Transcriptional and translational control in the Mammalian unfolded protein response.
2002,
Pubmed Harries,
The channel architecture of aquaporin 0 at a 2.2-A resolution.
2004,
Pubmed Horwitz,
Alpha-crystallin can function as a molecular chaperone.
1992,
Pubmed Jakob,
Small heat shock proteins are molecular chaperones.
1993,
Pubmed Jung,
Molecular structure of the water channel through aquaporin CHIP. The hourglass model.
1994,
Pubmed
,
Xenbase Kamsteeg,
An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus.
1999,
Pubmed
,
Xenbase Kaushal,
Structure and function in rhodopsin. 7. Point mutations associated with autosomal dominant retinitis pigmentosa.
1994,
Pubmed Kerr,
Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
1972,
Pubmed Kinoshita,
Aldose reductase in diabetic cataracts.
1981,
Pubmed KINOSHITA,
HYDRATION OF THE LENS DURING THE DEVELOPMENT OF GALACTOSE CATARACT.
1964,
Pubmed Kosinski-Collins,
In vitro unfolding, refolding, and polymerization of human gammaD crystallin, a protein involved in cataract formation.
2003,
Pubmed Kumari,
Functional expression and biophysical properties of polymorphic variants of the human gap junction protein connexin37.
2000,
Pubmed Kumari,
Site-directed mutations in the transmembrane domain M3 of human connexin37 alter channel conductance and gating.
2001,
Pubmed Kushmerick,
Ion, water and neutral solute transport in Xenopus oocytes expressing frog lens MIP.
1995,
Pubmed
,
Xenbase Kuwahara,
Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus.
2001,
Pubmed
,
Xenbase Kuwahara,
Transmembrane helix 5 is critical for the high water permeability of aquaporin.
1999,
Pubmed
,
Xenbase La Porta,
Adult murine CNS stem cells express aquaporin channels.
2006,
Pubmed Liu,
The unfolded protein response.
2003,
Pubmed Lomas,
Serpinopathies and the conformational dementias.
2002,
Pubmed Ma,
Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels.
1998,
Pubmed Manley,
Secondary structure and oligomerization of the E. coli glycerol facilitator.
2000,
Pubmed Marr,
Heteroligomerization of an Aquaporin-2 mutant with wild-type Aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus.
2002,
Pubmed Mathai,
Hourglass pore-forming domains restrict aquaporin-1 tetramer assembly.
1999,
Pubmed
,
Xenbase Mathias,
Physiological properties of the normal lens.
1997,
Pubmed Mathias,
The lens circulation.
2007,
Pubmed Mulders,
Water channel properties of major intrinsic protein of lens.
1995,
Pubmed
,
Xenbase Murata,
Structural determinants of water permeation through aquaporin-1.
2000,
Pubmed Németh-Cahalan,
pH and calcium regulate the water permeability of aquaporin 0.
2000,
Pubmed
,
Xenbase Okamura,
Bilateral congenital cataracts result from a gain-of-function mutation in the gene for aquaporin-0 in mice.
2003,
Pubmed Patil,
Expression of aquaporins in the rat ocular tissue.
1997,
Pubmed Pisano,
Genomic cloning, complete nucleotide sequence, and structure of the human gene encoding the major intrinsic protein (MIP) of the lens.
1991,
Pubmed Pitonzo,
Molecular mechanisms of aquaporin biogenesis by the endoplasmic reticulum Sec61 translocon.
2006,
Pubmed Preston,
Mutations in aquaporin-1 in phenotypically normal humans without functional CHIP water channels.
1994,
Pubmed
,
Xenbase Preston,
The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel.
1993,
Pubmed
,
Xenbase Preston,
Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein.
1992,
Pubmed
,
Xenbase Raman,
Chaperone-like activity and quaternary structure of alpha-crystallin.
1994,
Pubmed Ren,
Polymorphism in the packing of aquaporin-1 tetramers in 2-D crystals.
2000,
Pubmed Ren,
Visualization of a water-selective pore by electron crystallography in vitreous ice.
2001,
Pubmed Robben,
Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus.
2006,
Pubmed Rose,
Aquaporin 0-calmodulin interaction and the effect of aquaporin 0 phosphorylation.
2008,
Pubmed Roudier,
Erythroid expression and oligomeric state of the AQP3 protein.
2002,
Pubmed
,
Xenbase Ruiz-Ederra,
Accelerated cataract formation and reduced lens epithelial water permeability in aquaporin-1-deficient mice.
2006,
Pubmed Sandilands,
Altered aggregation properties of mutant gamma-crystallins cause inherited cataract.
2002,
Pubmed Schwartz,
Do all programmed cell deaths occur via apoptosis?
1993,
Pubmed Shepshelovich,
Protein synthesis inhibitors and the chemical chaperone TMAO reverse endoplasmic reticulum perturbation induced by overexpression of the iodide transporter pendrin.
2005,
Pubmed Shiels,
Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice.
2001,
Pubmed Shiels,
Disruption of lens fiber cell architecture in mice expressing a chimeric AQP0-LTR protein.
2000,
Pubmed Shiels,
Mutations in the founder of the MIP gene family underlie cataract development in the mouse.
1996,
Pubmed Sidjanin,
A 76-bp deletion in the Mip gene causes autosomal dominant cataract in Hfi mice.
2001,
Pubmed
,
Xenbase Spector,
Oxidative stress-induced cataract: mechanism of action.
1995,
Pubmed Stefani,
Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution.
2003,
Pubmed Sui,
Structural basis of water-specific transport through the AQP1 water channel.
,
Pubmed Swamy-Mruthinti,
Glycation decreases calmodulin binding to lens transmembrane protein, MIP.
2001,
Pubmed Swamy-Mruthinti,
Expression and characterization of lens membrane intrinsic protein, MIP, in a baculovirus expression system.
1998,
Pubmed Tamarappoo,
Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones.
1998,
Pubmed
,
Xenbase TROKEL,
The physical basis for transparency of the crystalline lens.
1962,
Pubmed van Hoek,
Purification and structure-function analysis of native, PNGase F-treated, and endo-beta-galactosidase-treated CHIP28 water channels.
1995,
Pubmed Varadaraj,
The role of MIP in lens fiber cell membrane transport.
1999,
Pubmed Varadaraj,
Functional expression of aquaporins in embryonic, postnatal, and adult mouse lenses.
2007,
Pubmed Varadaraj,
Regulation of aquaporin water permeability in the lens.
2005,
Pubmed
,
Xenbase Varadaraj,
Denaturants or cosolvents improve the specificity of PCR amplification of a G + C-rich DNA using genetically engineered DNA polymerases.
1994,
Pubmed Varadaraj,
Molecular characterization of four members of the alpha-tubulin gene family of the Bermuda land crab Gecarcinus lateralis.
1997,
Pubmed Varadaraj,
Actin-encoding cDNAs and gene expression during the intermolt cycle of the Bermuda land crab Gecarcinus lateralis.
1996,
Pubmed Verbavatz,
Tetrameric assembly of CHIP28 water channels in liposomes and cell membranes: a freeze-fracture study.
1993,
Pubmed Verkman,
Role of aquaporin water channels in eye function.
2003,
Pubmed Walz,
The three-dimensional structure of aquaporin-1.
1997,
Pubmed
,
Xenbase Willis,
Nucleotide sequence of an immediate-early frog virus 3 gene.
1984,
Pubmed Wistow,
Tandem sequence repeats in transmembrane channel proteins.
1991,
Pubmed Zampighi,
A method for determining the unitary functional capacity of cloned channels and transporters expressed in Xenopus laevis oocytes.
1995,
Pubmed
,
Xenbase
