Follistatin, an activin-binding protein, associates with heparan sulfate chains of proteoglycans on follicular granulosa cells.
Follistatin, an activin-binding protein secreted by cultured rat granulosa cells, was shown to associate with the cell surface by affinity labeling with 125I-activin. Addition of follistatin to the cultured cells demonstrated a typical ligand-binding saturation curve, suggesting that granulosa cells have a specific binding site for follistatin. This binding was markedly inhibited by heparin and heparan sulfate, but not by chondroitin sulfates A and C, keratan sulfate, and dermatan sulfate. When granulosa cells were treated with glycosaminoglycan-degrading enzymes before or after addition of follistatin to the cultures, heparinase and heparitinase treatments resulted in significant suppression of the binding, whereas treatment with chondroitinase ABC had no effect. A competition study of the binding using heparin derivatives demonstrated that follistatin seemed to recognize O-sulfate groups in the heparin molecule. Heparitinase-treated granulosa cells exhibited almost full responsiveness to activin, indicating that the enzyme treatment had no effect on activin and receptor interaction. These results suggest that follistatin/activin-binding protein binds to heparan sulfate side chains of proteoglycans on the granulosa cell surface to regulate the various actions of activin.
Frontier Research Program, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
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Nakamura
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Sugino
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Titani
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Sugino
D028341:Activins; D000345:Affinity Labels; D000818:Animals; D001667:Binding, Competitive; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D038681:Follistatin; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism*; D007265:Inhibins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011974:Receptors, LH / Q000032:analysis; D015398:Signal Transduction
D028341:Activins; D000345:Affinity Labels; D011508:Chondroitin Sulfate Proteoglycans; D006063:Chorionic Gonadotropin; D038681:Follistatin; D006023:Glycoproteins; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D007265:Inhibins; D011974:Receptors, LH