A direct role for phosphatidylinositol-4,5-bisphosphate in unconventional secretion of fibroblast growth factor 2
Temmerman, Koen, Ebert, Antje D., Müller, Hans-Michael, Sinning, Irmgard, Tews, Ivo and Nickel, Walter (2008) A direct role for phosphatidylinositol-4,5-bisphosphate in unconventional secretion of fibroblast growth factor 2. Traffic, 9, (7), 1204-1217. (doi:10.1111/j.1600-0854.2008.00749.x). (PMID:18419755).
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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.
|Digital Object Identifier (DOI):||doi:10.1111/j.1600-0854.2008.00749.x|
|Keywords:||fibroblast growth factor 2, membrane translocation, phosphatidylinositol-4,5-bisphosphate, phosphoinositides, protein–lipid interaction, protein targeting, unconventional protein secretion|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Divisions:||Faculty of Natural and Environmental Sciences > Biological Sciences
|Date Deposited:||26 Oct 2011 10:51|
|Last Modified:||27 Mar 2014 19:46|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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