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A Direct Role for Phosphatidylinositol‐4,5‐bisphosphate in Unconventional Secretion of Fibroblast Growth Factor 2
Author(s) -
Temmerman Koen,
Ebert Antje D,
Müller HansMichael,
Sinning Irmgard,
Tews Ivo,
Nickel Walter
Publication year - 2008
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2008.00749.x
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , biology , phosphatidylinositol , fibroblast growth factor , phosphatidylinositol 4,5 bisphosphate , secretion , cytoplasm , golgi apparatus , secretory pathway , diacylglycerol kinase , extracellular , biochemistry , signal transduction , receptor , protein kinase c
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)P 2 ], 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)P 2 is shown to depend on a lipid background that resembles plasma membranes. We show that the interaction with PI(4,5)P 2 is critically important for FGF‐2 secretion as experimental conditions reducing cellular levels of PI(4,5)P 2 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)P 2 that were found to be severely impaired with regard to export efficiency. These data show that a transient interaction with PI(4,5)P 2 associated with the inner leaflet of plasma membranes represents the initial step of the unconventional secretory pathway of FGF‐2.