Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6- O -sulfotransferase
| Autor: | Tomoya O. Akama, Bruce Caterson, Andrew J. Quantock, Jun Nakayama, Keith M. Meek, Robert D. Young, Clare Elizabeth Hughes, Briedgeen Kerr, Nicola Beecher, Philip N. Lewis, Yasuo Tano, Yasutaka Hayashida, Michiko N. Fukada, Kohji Nishida, Akira Tanigami |
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| Rok vydání: | 2006 |
| Předmět: |
Heterozygote
Lumican Keratan sulfate Dermatan sulfate Cornea Extracellular matrix Glycosaminoglycan Mice chemistry.chemical_compound Sulfation X-Ray Diffraction Morphogenesis medicine Animals Chondroitin sulfate Mice Knockout Multidisciplinary Homozygote Biological Sciences Extracellular Matrix Cell biology medicine.anatomical_structure chemistry Biochemistry Keratan Sulfate sense organs Sulfotransferases |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:13333-13338 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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