Glypican-1 drives unconventional secretion of Fibroblast Growth Factor 2
- Heidelberg University, Germany
- Freie Universität Berlin, Germany
Abstract
Fibroblast Growth Factor 2 (FGF2) is a tumor cell survival factor that is transported into the extracellular space by an unconventional secretory mechanism. Cell surface heparan sulfate proteoglycans are known to play an essential role in this process. Unexpectedly, we found that among the diverse sub-classes consisting of syndecans, perlecans, glypicans and others, Glypican-1 (GPC1) is the principle and rate-limiting factor that drives unconventional secretion of FGF2. By contrast, we demonstrate GPC1 to be dispensable for FGF2 signaling into cells. We provide first insights into the structural basis for GPC1-dependent FGF2 secretion, identifying disaccharides with N-linked sulfate groups to be enriched in the heparan sulfate chains of GPC1 to which FGF2 binds with high affinity. Our findings have broad implications for the role of GPC1 as a key molecule in tumor progression.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for various Figures being provided in a compressed zip file.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (SFB/TRR 83 - A5)
- Carola Sparn
- Walter Nickel
Deutsche Forschungsgemeinschaft (SFB/TRR 186 - A1)
- Eleni Dimou
- Annalena Meyer
- Roberto Saleppico
- Helge Ewers
- Walter Nickel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Adam Linstedt, Carnegie Mellon University, United States
Version history
- Preprint posted: November 12, 2021 (view preprint)
- Received: November 14, 2021
- Accepted: March 24, 2022
- Accepted Manuscript published: March 29, 2022 (version 1)
- Version of Record published: April 6, 2022 (version 2)
Copyright
© 2022, Sparn et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Glypican-1 drives unconventional secretion of Fibroblast Growth Factor 2
eLife 11:e75545.
https://doi.org/10.7554/eLife.75545
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