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|Title:||Nance-Horan syndrome protein, NHS, associates with epithelial cell junctions|
|Citation:||Human Molecular Genetics, 2006; 15(12):1972-1983|
|Publisher:||Oxford Univ Press|
|Shiwani Sharma, Sharyn L. Ang, Marie Shaw, David A. Mackey, Jozef Gécz, John W. McAvoy and Jamie E. Craig|
|Abstract:||Nance-Horan syndrome, characterized by congenital cataracts, craniofacial, dental abnormalities and mental disturbances, is an X-linked disorder with significant phenotypic heterogeneity. Affected individuals have mutations in the NHS (Nance-Horan syndrome) gene typically resulting in premature truncation of the protein. This report underlines the complexity of the regulation of the NHS gene that transcribes several isoforms. We demonstrate the differential expression of the two NHS isoforms, NHS-A and NHS-1A, and differences in the subcellular localization of the proteins encoded by these isoforms. This may in part explain the pleiotropic features of the syndrome. We show that the endogenous and exogenous NHS-A isoform localizes to the cell membrane of mammalian cells in a cell-type-dependent manner and that it co-localizes with the tight junction (TJ) protein ZO-1 in the apical aspect of cell membrane in epithelial cells. We also show that the NHS-1A isoform is a cytoplasmic protein. In the developing mammalian lens, we found continuous expression of NHS that became restricted to the lens epithelium in pre- and postnatal lens. Consistent with the in vitro findings, the NHS-A isoform associates with the apical cell membrane in the lens epithelium. This study suggests that disturbances in intercellular contacts underlie cataractogenesis in the Nance-Horan syndrome. NHS is the first gene localized at TJs that has been implicated in congenital cataracts.|
|Keywords:||Lens, Crystalline; Cell Line; Cell Membrane; Tight Junctions; Fibroblasts; Epithelial Cells; Animals; Humans; Mice; Cataract; Genetic Diseases, X-Linked; Syndrome; Membrane Proteins; Nuclear Proteins; Phosphoproteins; Protein Isoforms; Transfection; Gene Expression Regulation, Developmental; Zonula Occludens-1 Protein|
|Rights:||© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org|
|Appears in Collections:||Paediatrics publications|
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