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.
Nakamura
T
T
Frontier Research Program, Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Sugino
K
K
Titani
K
K
Sugino
H
H
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