Details

Autor(en) / Beteiligte

• Temmerman, Koen
• Ebert, Antje D
• Müller, Hans-Michael
• Sinning, Irmgard
• Tews, Ivo
• Nickel, Walter

Titel

Direct Role for Phosphatidylinositol-4,5-bisphosphate in Unconventional Secretion of Fibroblast Growth Factor 2

Ist Teil von

• Traffic (Copenhagen, Denmark), 2008-07, Vol.9 (7), p.1204-1217

Ort / Verlag

Oxford, UK: Oxford, UK : Blackwell Publishing Ltd

Erscheinungsjahr

2008

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Fibroblast growth factor 2 (FGF-2) is a mitogen that is exported from cells by an endoplasmic reticulum/Golgi-independent secretory pathway. Recent findings have shown that FGF-2 export occurs by direct translocation from the cytoplasm across the plasma membrane into the extracellular space. Here, we report that FGF-2 contains a binding site for phosphatidylinositol-4,5-bisphosphate [PI(4,5)P₂], the principal phosphoinositide species associated with plasma membranes. Intriguingly, in the context of a lipid bilayer, the interaction between FGF-2 and PI(4,5)P₂ is shown to depend on a lipid background that resembles plasma membranes. We show that the interaction with PI(4,5)P₂ is critically important for FGF-2 secretion as experimental conditions reducing cellular levels of PI(4,5)P₂ resulted in a substantial drop in FGF-2 export efficiency. Likewise, we have identified FGF-2 variant forms deficient for binding to PI(4,5)P₂ that were found to be severely impaired with regard to export efficiency. These data show that a transient interaction with PI(4,5)P₂ associated with the inner leaflet of plasma membranes represents the initial step of the unconventional secretory pathway of FGF-2.