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Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2
Open accessAbstract
FGF-2 is an unconventionally secreted lectin that transmits proangiogenic signals through a ternary complex with high-affinity FGF receptors and heparan sulfate proteoglycans (HSPGs). Although FGF-2 signal transduction is understood in great detail, its mechanism of release from cells, which is independent of the classical secretory pathway, remains elusive. To test the hypothesis that FGF-2 secretion is linked to its cell-surface ligands, we studied FGF-2 release using mutants defective for HSPG binding and cells with impaired HSPG biosynthesis. Here, we report that a functional interaction between FGF-2 and HSPGs is required for net export of FGF-2 from mammalian cells. FGF-2 release requires extracellular, membrane-proximal HSPGs. We propose that extracellular HSPGs form a molecular trap that drives FGF-2 translocation across the plasma membrane.
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Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79
Lolicato, F., Steringer, J., Saleppico, R., Beyer, D., Fernandez-Sobaberas, J., Unger, S., Klein, S., Riegerová, P., Wegehingel, S., Müller, H., et al. (2023) · doi:10.7554/elife.88579.2 · Cited by 1
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Metadata
- Authors
- Zehe, C., Engling, A., Wegehingel, S., Schäfer, T., & Nickel, W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-10-17
- Volume
- 103
- Issue
- 42
- Pages
- 15479-15484
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2044655036
- Cited by
- 161
- References
- 0
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- green
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- Zehe, C., Engling, A., Wegehingel, S., Schäfer, T., & Nickel, W. (2006). Cell-surface heparan sulfate proteoglycans are essential components of the unconventional export machinery of FGF-2. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0605997103
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