title: Structural function of MIP/aquaporin 0 in the eye lens; genetic defects lead to congenital inherited cataracts.
abstract: Aquaporin 0 (AQP0) was originally characterized as a membrane intrinsic protein, specifically expressed in the lens fibers of the ocular lens and designated MIP, for major intrinsic protein of the lens. Once the gene was cloned, an internal repeat was identified, encoding for the amino acids Asp-Pro-Ala, the NPA repeat. Shortly, the MIP gene family was emerging, with members being characterized in mammals, insects, and plants. Once Peter Agre's laboratory developed a functional assay for water channels, the MIP family became the aquaporin family and MIP became known as aquaporin 0. Besides functioning as a water channel, aquaporin 0 also plays a structural role, being required for maintaining the transparency and optical accommodation of the ocular lens. Mutations in the AQP0 gene in human and mice result in genetic cataracts; deletion of the MIP/AQP0 gene in mice results in lack of suture formation required for maintenance of the lens fiber architecture, resulting in perturbed accommodation and focus properties of the ocular lens. Crystallography studies support the notion of the double function of aquaporin 0 as a water channel (open configuration) or adhesion molecule (closed configuration) in the ocular lens fibers. The functions of MIP/AQP0, both as a water channel and an adhesive molecule in the lens fibers, contribute to the narrow intercellular space of the lens fibers that is required for lens transparency and accommodation.
authors.affiliation: National Institutes of Health, National Eye Institute, Bldg. 31, Room 6A-32, Bethesda, MD, 20892-2510, USA. abc@helix.nih.gov
authors.forename: Ana B
authors.initials: AB
authors.lastname: Chepelinsky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020346:Aquaporins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002386:Cataract / Q000151:congenital / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D003459:Crystallins / Q000378:metabolism; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D014867:Water / Q000378:metabolism
chemical_list: D020346:Aquaporins; D015815:Cell Adhesion Molecules; D003459:Crystallins; D005136:Eye Proteins; C030328:aquaporin 0; D014867:Water