Abstract

Movement of water across the plasma membrane is critical to the functions of several tissues in eye. Nevertheless, the molecular structures responsible for water transport were enigmatic until the recent discovery of CHIP (AQP1) and other members of the aquaporin family of membrane water channel proteins. Multiple aquaporins are being identified in eye: AQP1 is in nonpigmented ciliary epithelium, corneal endothelium, lens epithelium, and trabecular meshwork; AQP4 is in neurons; AQP5 is in corneal epithelium, lacrimal and salivary glands; AQP6 is in retinal pigmented epithelium. Analyses of these proteins may now provide molecular insight into water transport during normal vision and in several diseases of eye. I. Genetic studies. Human, murine, and bovine cDNAs for AQP5 will be isolated and compared for conservation of residues potentially important to function, The AQP5 gene(s) will be cloned from human and mouse genomic libraries, their organization, copy number, and chromosomal locations will be established. AQP6 and other novel partial cDNAs from eye will be genetically characterized similarly. II. Distribution and expression studies. The cellular and subcellular location of AQPs 1, 4, 5, and 6 will be precisely established in normal ocular tissues by immunohistochemistry and immunoelectronmicroscopy. Constitutive expression of these AQPs will be studied in murine ocular tissues during fetal development and in response to pharmacologic and hormonal stimuli. III. Patient studies. Patients with knockout mutations in AQP1 will be examined for visual disturbances. Patient samples from the recent Collaborative Corneal Transplant Study will be examined for incompatibles in the Colton blood group antigens which may contribute to graft rejection, since these are protein polymorphisms within AQP1 which is abundant in cornea. Immunohistochemical distributions of AQPs 1, 4, 5, and 6 will be assessed in tissues from pathological specimens including corneal dystrophies, open angle glaucomas, retinal deteriorations, and aging. Serum and lymphocytes from patients with Sjogren's syndrome will be examined for evidence of immune responses to AQP5.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY011239-02
Application #
2331669
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1996-02-01
Project End
2000-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Rash, J E (2010) Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system. Neuroscience 168:982-1008
Huang, Chunyi George; Lamitina, Todd; Agre, Peter et al. (2007) Functional analysis of the aquaporin gene family in Caenorhabditis elegans. Am J Physiol Cell Physiol 292:C1867-73
Huang, Chunyi George; Agre, Peter; Strange, Kevin et al. (2006) Isolation of C. elegans deletion mutants following ENU mutagenesis and thermostable restriction enzyme PCR screening. Mol Biotechnol 32:83-6
Beitz, Eric; Liu, Kun; Ikeda, Masahiro et al. (2006) Determinants of AQP6 trafficking to intracellular sites versus the plasma membrane in transfected mammalian cells. Biol Cell 98:101-9
Liu, Kun; Nagase, Hiroaki; Huang, Chunyi George et al. (2006) Purification and functional characterization of aquaporin-8. Biol Cell 98:153-61
Eid, Tore; Lee, Tih-Shih W; Thomas, Marion J et al. (2005) Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus. Proc Natl Acad Sci U S A 102:1193-8
Liu, Kun; Kozono, David; Kato, Yasuhiro et al. (2005) Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution. Proc Natl Acad Sci U S A 102:2192-7
Liu, Zijuan; Carbrey, Jennifer M; Agre, Peter et al. (2004) Arsenic trioxide uptake by human and rat aquaglyceroporins. Biochem Biophys Res Commun 316:1178-85
Hazama, Akihiro; Kozono, David; Guggino, William B et al. (2002) Ion permeation of AQP6 water channel protein. Single channel recordings after Hg2+ activation. J Biol Chem 277:29224-30
Nejsum, Lene N; Kwon, Tae-Hwan; Jensen, Uffe B et al. (2002) Functional requirement of aquaporin-5 in plasma membranes of sweat glands. Proc Natl Acad Sci U S A 99:511-6

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