Glypican-1 drives unconventional secretion of fibroblast growth factor 2.
biochemistry
biochemistry of biological membranes
cell biology
chemical biology
fibroblast growth factor 2
glypican
human
phosphoinositides
protein translocation across membranes
unconventional protein secretion
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
29 03 2022
29 03 2022
Historique:
received:
14
11
2021
accepted:
24
03
2022
pubmed:
30
3
2022
medline:
9
4
2022
entrez:
29
3
2022
Statut:
epublish
Résumé
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 subclasses 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.
Identifiants
pubmed: 35348113
doi: 10.7554/eLife.75545
pii: 75545
pmc: PMC8986318
doi:
pii:
Substances chimiques
Glypicans
0
Heparan Sulfate Proteoglycans
0
Fibroblast Growth Factor 2
103107-01-3
Heparitin Sulfate
9050-30-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, Sparn et al.
Déclaration de conflit d'intérêts
CS, ED, AM, RS, SW, MG, SK, HE, WN No competing interests declared
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