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A direct role for phosphatidylinositol-4,5-bisphosphate in unconventional secretion of fibroblast growth factor 2

Record type: Article

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.

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Citation

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), pp. 1204-1217. (doi:10.1111/j.1600-0854.2008.00749.x). (PMID:18419755).

More information

e-pub ahead of print date: 28 June 2008
Published date: July 2008
Keywords: fibroblast growth factor 2, membrane translocation, phosphatidylinositol-4, 5-bisphosphate, phosphoinositides, protein–lipid interaction, protein targeting, unconventional protein secretion
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 200525
URI: http://eprints.soton.ac.uk/id/eprint/200525
ISSN: 1398-9219
PURE UUID: 81078dc7-b7ac-4799-841f-b2c1ab4a4db1
ORCID for Ivo Tews: ORCID iD orcid.org/0000-0002-4704-1139

Catalogue record

Date deposited: 26 Oct 2011 10:51
Last modified: 18 Jul 2017 11:14

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Contributors

Author: Koen Temmerman
Author: Antje D. Ebert
Author: Hans-Michael Müller
Author: Irmgard Sinning
Author: Ivo Tews ORCID iD
Author: Walter Nickel

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