Matrix Morphogenesis in Cornea is Mediated by the Modification of Keratan Sulfate by Glcnac 6-o-sulfotransferase.
From: Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Sep 2006
- ISSN: 0027-8424
- Volume: 103
- Issue: 36
- Pages: 13333-8
- Medium: Print
- Language: English
- Citation (JAMA): Hayashida Yasutaka, Akama Tomoya O, Beecher Nicola, et al. Matrix Morphogenesis in Cornea is Mediated by the Modification of Keratan Sulfate by Glcnac 6-o-sulfotransferase.. Proc. Natl. Acad. Sci. U.S.A. Sep 2006;103:13333-8
Abstract
Matrix assembly and homeostasis in collagen-rich tissues are mediated by interactions with proteoglycans (PGs) substituted with sulfated glycosaminoglycans (GAGs). The major GAG in cornea is keratan sulfate (KS), which is N-linked to one of three PG core proteins. To ascertain the importance of the carbohydrate chain sulfation step in KS functionality, we generated a strain of mice with a targeted gene deletion in Chst5, which encodes an N-acetylglucosamine-6-O-sulfotransferase that is integral to the sulfation of KS chains. Corneas of homozygous mutants were significantly thinner than those of WT or heterozygous mice. They lacked high-sulfated KS, but contained the core protein of the major corneal KSPG, lumican. Histochemically stained KSPGs coassociated with fibrillar collagen in WT corneas, but were not identified in the Chst5-null tissue. Conversely, abnormally large chondroitin sulfate/dermatan sulfate PG complexes were abundant throughout the Chst5-deficient cornea, indicating an alteration of controlled PG production in the mutant cornea. The corneal stroma of the Chst5-null mouse exhibited widespread structural alterations in collagen fibrillar architecture, including decreased interfibrillar spacing and a more spatially disorganized collagen array. The enzymatic sulfation of KS GAG chains is thus identified as a key requirement for PG biosynthesis and collagen matrix organization.
Mesh Headings (Keywords): Animals, Cornea, Extracellular Matrix, Heterozygote, Homozygote, Keratan Sulfate, Mice, Mice, Knockout, Morphogenesis, Sulfotransferases, X-Ray Diffraction
Check for Full Text / PubMed Unique Identifier (PMID): 16938851
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