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

Simona Taverna, Salvatrice Rigogliuso, Giuseppe Pizzolanti, Giulio Ghersi, Antonio Pavan, Marco Presta, Giuseppe Pizzolanti, Vincenza Dolo, Patrizia Dell'Era, Maria Letizia Vittorelli, Paolo Mignatti, Maria Letizia Vittorelli

Risultato della ricerca: Articlepeer review

91 Citazioni (Scopus)

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 down-regulated, 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
Lingua originaleEnglish
pagine (da-a)51911-51919
Numero di pagine9
RivistaTHE JOURNAL OF BIOLOGICAL CHEMISTRY
Volume278
Stato di pubblicazionePublished - 2003

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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