Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Phosphorylation determines the calmodulin-mediated Ca2+ response and water permeability of AQP0.
Kalman K
,
Németh-Cahalan KL
,
Froger A
,
Hall JE
.
???displayArticle.abstract???
In Xenopus oocytes, the water permeability of AQP0 (P(f)) increases with removal of external calcium, an effect that is mediated by cytoplasmic calmodulin (CaM) bound to the C terminus of AQP0. To investigate the effects of serine phosphorylation on CaM-mediated Ca(2+) regulation of P(f), we tested the effects of kinase activation, CaM inhibition, and a series of mutations in the C terminus CaM binding site. Calcium regulation of AQP0 P(f) manifests four distinct phenotypes: Group 1, with high P(f) upon removal of external Ca(2+) (wild-type, S229N, R233A, S235A, S235K, K238A, and R241E); Group 2, with high P(f) in elevated (5 mm) external Ca(2+) (S235D and R241A); Group 3, with high P(f) and no Ca(2+) regulation (S229D, S231N, S231D, S235N, and S235N/I236S); and Group 4, with low P(f) and no Ca(2+) regulation (protein kinase A and protein kinase C activators, S229D/S235D and S235N/I236S). Within each group, we tested whether CaM binding mediates the phenotype, as shown previously for wild-type AQP0. In the presence of calmidazolium, a CaM inhibitor, S235D showed high P(f) and no Ca(2+) regulation, suggesting that S235D still binds CaM. Contrarily, S229D showed a decrease in recruitment of CaM, suggesting that S229D is unable to bind CaM. Taken together, our results suggest a model in which CaM acts as an inhibitor of AQP0 P(f). CaM binding is associated with a low P(f) state, and a lack of CaM binding is associated with a high P(f) state. Pathological conditions of inappropriate phosphorylation or calcium/CaM regulation could induce P(f) changes contributing to the development of a cataract.
Al-Ghoul,
Lens structure in MIP-deficient mice.
2003, Pubmed
Al-Ghoul,
Lens structure in MIP-deficient mice.
2003,
Pubmed
Ball,
Post-translational modifications of aquaporin 0 (AQP0) in the normal human lens: spatial and temporal occurrence.
2004,
Pubmed
Donaldson,
Molecular solutions to mammalian lens transparency.
2001,
Pubmed
Ervin,
Phosphorylation and glycosylation of bovine lens MP20.
2005,
Pubmed
Francis,
Congenital progressive polymorphic cataract caused by a mutation in the major intrinsic protein of the lens, MIP (AQP0).
2000,
Pubmed
Garland,
Phosphorylation of lens fiber cell membrane proteins.
1985,
Pubmed
Girsch,
Calmodulin interacts with a C-terminus peptide from the lens membrane protein MIP26.
1991,
Pubmed
Gonen,
Lipid-protein interactions in double-layered two-dimensional AQP0 crystals.
2005,
Pubmed
Hanson,
The major in vivo modifications of the human water-insoluble lens crystallins are disulfide bonds, deamidation, methionine oxidation and backbone cleavage.
2000,
Pubmed
Harries,
The channel architecture of aquaporin 0 at a 2.2-A resolution.
2004,
Pubmed
Iyengar,
Duration of ERK1/2 phosphorylation induced by FGF or ocular media determines lens cell fate.
2007,
Pubmed
Johnson,
A lens intercellular junction protein, MP26, is a phosphoprotein.
1986,
Pubmed
Kalman,
AQP0-LTR of the Cat Fr mouse alters water permeability and calcium regulation of wild type AQP0.
2006,
Pubmed
,
Xenbase
Lan,
The role of calmodulin-binding sites in the regulation of the Drosophila TRPL cation channel expressed in Xenopus laevis oocytes by ca2+, inositol 1,4,5-trisphosphate and GTP-binding proteins.
1998,
Pubmed
,
Xenbase
Lin,
PKCgamma knockout mouse lenses are more susceptible to oxidative stress damage.
2006,
Pubmed
Lin,
A substitution of arginine to lysine at the COOH-terminus of MIP caused a different binocular phenotype in a congenital cataract family.
2007,
Pubmed
Maddala,
Lens fiber cell elongation and differentiation is associated with a robust increase in myosin light chain phosphorylation in the developing mouse.
2007,
Pubmed
Mathias,
Physiological properties of the normal lens.
1997,
Pubmed
Mathias,
The lens: local transport and global transparency.
2004,
Pubmed
Mathias,
The lens circulation.
2007,
Pubmed
Németh-Cahalan,
Zinc modulation of water permeability reveals that aquaporin 0 functions as a cooperative tetramer.
2007,
Pubmed
,
Xenbase
Németh-Cahalan,
pH and calcium regulate the water permeability of aquaporin 0.
2000,
Pubmed
,
Xenbase
Németh-Cahalan,
Molecular basis of pH and Ca2+ regulation of aquaporin water permeability.
2004,
Pubmed
,
Xenbase
Preston,
Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein.
1992,
Pubmed
,
Xenbase
Rose,
Aquaporin 0-calmodulin interaction and the effect of aquaporin 0 phosphorylation.
2008,
Pubmed
Shiels,
Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice.
2001,
Pubmed
Shiels,
Mutations in the founder of the MIP gene family underlie cataract development in the mouse.
1996,
Pubmed
Shiels,
Disruption of lens fiber cell architecture in mice expressing a chimeric AQP0-LTR protein.
2000,
Pubmed
Sue Menko,
Lens epithelial cell differentiation.
2002,
Pubmed
Varadaraj,
Regulation of aquaporin water permeability in the lens.
2005,
Pubmed
,
Xenbase
Zampighi,
Regulation of lens cell-to-cell communication by activation of PKCgamma and disassembly of Cx50 channels.
2005,
Pubmed
