Fibroblast growth factor-2 (FGF-2), a polypeptide with regulatory activity on cell growth and differentiation, lacks a conventional secretory signal sequence, and its mechanism of release from cells remains unclear. We characterized the role of extracellular vesicle shedding in FGF-2 release. Viable cells released membrane vesicles in the presence of serum. However, in serum-free medium vesicle shedding was dramatically downregulated, and the cells did not release FGF-2 activity into their conditioned medium. Addition of serum to serum-starved cells rapidly induced intracellular FGF-2 clustering under the plasma membrane and into granules that colocalized with patches of the cell membrane with typical features of shed vesicle membranes. Shed vesicles carried three FGF-2 isoforms ( 18, 22, 24 kDa). Addition of vesicles to endothelial cells stimulated chemotaxis and urokinase plasminogen activator production, which were blocked by anti-FGF-2 antibodies. Treatment of intact vesicles with 2.0 M NaCl or heparinase, which release FGF-2 from membrane-bound proteoglycans, did not abolish their stimulatory effect on endothelial cells, indicating that FGF-2 is carried inside vesicles. The comparison of the stimulatory effects of shed vesicles and vesicle-free conditioned medium showed that vesicles represent a major reservoir of FGF-2. Thus, FGF-2 can be released from cells through vesicle shedding.

Shedding of membrane vesicles mediates fibroblast growth factor-2 release from cells / S., Taverna; G., Ghersi; A., Ginsetra; S., Rigogliuso; S., Pecorella; Alaimo, Giovanna; F., Saladino; V., Dolo; P., Dell'Era; Pavan, Antonio; G., Pizzolanti; P., Mignatti; M., Presta; M. L., Vittorelli. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 278:51(2003), pp. 51911-51919. [10.1074/jbc.m304192200]

Shedding of membrane vesicles mediates fibroblast growth factor-2 release from cells

ALAIMO, Giovanna;PAVAN, Antonio;
2003

Abstract

Fibroblast growth factor-2 (FGF-2), a polypeptide with regulatory activity on cell growth and differentiation, lacks a conventional secretory signal sequence, and its mechanism of release from cells remains unclear. We characterized the role of extracellular vesicle shedding in FGF-2 release. Viable cells released membrane vesicles in the presence of serum. However, in serum-free medium vesicle shedding was dramatically downregulated, and the cells did not release FGF-2 activity into their conditioned medium. Addition of serum to serum-starved cells rapidly induced intracellular FGF-2 clustering under the plasma membrane and into granules that colocalized with patches of the cell membrane with typical features of shed vesicle membranes. Shed vesicles carried three FGF-2 isoforms ( 18, 22, 24 kDa). Addition of vesicles to endothelial cells stimulated chemotaxis and urokinase plasminogen activator production, which were blocked by anti-FGF-2 antibodies. Treatment of intact vesicles with 2.0 M NaCl or heparinase, which release FGF-2 from membrane-bound proteoglycans, did not abolish their stimulatory effect on endothelial cells, indicating that FGF-2 is carried inside vesicles. The comparison of the stimulatory effects of shed vesicles and vesicle-free conditioned medium showed that vesicles represent a major reservoir of FGF-2. Thus, FGF-2 can be released from cells through vesicle shedding.
2003
01 Pubblicazione su rivista::01a Articolo in rivista
Shedding of membrane vesicles mediates fibroblast growth factor-2 release from cells / S., Taverna; G., Ghersi; A., Ginsetra; S., Rigogliuso; S., Pecorella; Alaimo, Giovanna; F., Saladino; V., Dolo; P., Dell'Era; Pavan, Antonio; G., Pizzolanti; P., Mignatti; M., Presta; M. L., Vittorelli. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 278:51(2003), pp. 51911-51919. [10.1074/jbc.m304192200]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/284
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