A direct role for phosphatidylinositol-4,5-bisphosphate in unconventional secretion of fibroblast growth factor 2
A direct role for phosphatidylinositol-4,5-bisphosphate in unconventional secretion of fibroblast growth factor 2
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.
fibroblast growth factor 2, membrane translocation, phosphatidylinositol-4, 5-bisphosphate, phosphoinositides, protein–lipid interaction, protein targeting, unconventional protein secretion
1204-1217
Temmerman, Koen
d20079dc-4ca9-4fd2-9a0c-26cd57277d97
Ebert, Antje D.
a13567ca-ad45-4e1f-8451-0449a6e555e2
Müller, Hans-Michael
3f4844bc-3770-4883-accc-62f2dff93936
Sinning, Irmgard
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Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Nickel, Walter
ccabdc92-e871-48e1-9960-5164e8587513
July 2008
Temmerman, Koen
d20079dc-4ca9-4fd2-9a0c-26cd57277d97
Ebert, Antje D.
a13567ca-ad45-4e1f-8451-0449a6e555e2
Müller, Hans-Michael
3f4844bc-3770-4883-accc-62f2dff93936
Sinning, Irmgard
fbc3f199-8a3b-47a6-9ee7-00bfc472e079
Tews, Ivo
9117fc5e-d01c-4f8d-a734-5b14d3eee8dd
Nickel, Walter
ccabdc92-e871-48e1-9960-5164e8587513
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), .
(doi:10.1111/j.1600-0854.2008.00749.x).
(PMID:18419755)
Abstract
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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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
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Local EPrints ID: 200525
URI: http://eprints.soton.ac.uk/id/eprint/200525
ISSN: 1398-9219
PURE UUID: 81078dc7-b7ac-4799-841f-b2c1ab4a4db1
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Date deposited: 26 Oct 2011 10:51
Last modified: 15 Mar 2024 03:36
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Author:
Koen Temmerman
Author:
Antje D. Ebert
Author:
Hans-Michael Müller
Author:
Irmgard Sinning
Author:
Walter Nickel
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