Structure and Function of Basement Membrane Proteoglycans

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Abstract
Basement membranes contain at least three different proteoglycans. These are a large, low buoyant density heparan sulphate proteoglycan and two smaller, high density proteoglycans with either heparan sulphate or chondroitin sulphate side-chains. The large (Mr 400K–600K and small (Mr 130K) heparan sulphate proteoglycans were purified from the mouse EHS tumour. These proteoglycans are immunologically related by sharing some protein core antigenic determinants (epitopes) but do not cross-react with cell-surface heparan sulphate proteoglycans or with proteoglycans from interstitial connective tissue. This indicates that they belong to a distinct family of proteoglycans. Structural models were developed, based on electron microscopy and analytical ultracentri-fugation, demonstrating that the small proteoglycan contains on average four heparan sulphate chains of about 30 nm in length, while the large proteoglycan consists of three long (about 90 nm) heparan sulphate chains connected to one end of a large core protein. Single heparan sulphate chains were isolated from the EHS turnour proteoglycans and from the corresponding proteoglycans from Reichert's membrane of the mouse embryo. The heparan sulphate from Reichert's membrane bound to anti-thrombin with high affinity and was found to contain the unique 3-0-sulphated glucosamine residue previously identified in the antithrombin-binding region of heparin. The EHS tumour heparan sulphate showed a higher N-lO-sulphate ratio and a lower affinity for antithrombin.