title: Electron tomography reveals multiple self-association of chondroitin sulphate/dermatan sulphate proteoglycans in Chst5-null mouse corneas.
abstract: The spatial distribution of collagen fibrils in the corneal stroma is essential for corneal transparency and is primarily regulated by extrafibrillar proteoglycans, which are multi-functional polymers that interact with hybrid type I/V collagen fibrils. In order to understand more about proteoglycan organisation and collagen associations in the cornea, three-dimensional electron microscopy reconstructions of collagen-proteoglycan interactions in the anterior, mid and posterior stroma from a Chst5 knockout mouse, which lacks a keratan sulphate sulphotransferase, were obtained. Both longitudinal and transverse section show sinuous, oversized proteoglycans with near-periodic, orthogonal off-shoots. In many cases, these proteoglycans traverse over 400nm of interfibrillar space interconnecting over 10 collagen fibrils. The reconstructions suggest that multiple chondroitin sulphate/dermatan sulphate proteoglycans have aggregated laterally and, possibly, end-to-end, with orthogonal extensions protruding from the main electron-dense stained filament. We suggest possible mechanisms as to how sulphation differences may lead to this increase in aggregation of proteoglycans in the Chst5-null mouse corneal stroma and how this relates to proteoglycan packing in healthy corneas.
authors: Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Wales, UK. ParfittGJ1@cf.ac.uk
authors: Geraint J
authors: GJ
authors: Parfitt
authors: Christian
authors: C
authors: Pinali
authors: Tomoya O
authors: TO
authors: Akama
authors: Robert D
authors: RD
authors: Young
authors: Kohji
authors: K
authors: Nishida
authors: Andrew J
authors: AJ
authors: Quantock
authors: Carlo
authors: C
authors: Knupp
mesh_terms: D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry*; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003315:Cornea / Q000737:chemistry* / Q000648:ultrastructure; D003871:Dermatan Sulfate / Q000737:chemistry*; D055032:Electron Microscope Tomography / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D015394:Molecular Structure; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D000097811:Carbohydrate Sulfotransferases
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C032649:dermatan sulfate proteoglycan