Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6-O-sulfotransferase

Hayashida, Yasutaka, Akama, Tomoya O., Beecher, Nicola, Lewis, Philip ORCID: https://orcid.org/0000-0002-3353-0708, Young, Robert David ORCID: https://orcid.org/0000-0002-8300-8002, Meek, Keith Michael Andrew ORCID: https://orcid.org/0000-0002-9948-7538, Kerr, Briedgeen, Hughes, Clare Elizabeth ORCID: https://orcid.org/0000-0003-4726-5877, Caterson, Bruce ORCID: https://orcid.org/0000-0001-6016-0661, Tanigami, Akira, Nakayama, Jun, Fukada, Michiko N., Tano, Yasuo, Nishida, Kohji and Quantock, Andrew James ORCID: https://orcid.org/0000-0002-2484-3120 2006. Matrix morphogenesis in cornea is mediated by the modification of keratan sulfate by GlcNAc 6-O-sulfotransferase. PNAS 103 (36) , pp. 13333-13338. 10.1073/pnas.0605441103

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences
ISSN:	00278424
Last Modified:	01 Mar 2024 07:47
URI:	https://orca.cardiff.ac.uk/id/eprint/863

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