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Roles of two types of heparan sulfate clusters in Wnt distribution and signaling in Xenopus
- Source :
- Nature Communications, Vol 8, Iss 1, Pp 1-19 (2017), Nature Communications
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Wnt proteins direct embryonic patterning, but the regulatory basis of their distribution and signal reception remain unclear. Here, we show that endogenous Wnt8 protein is distributed in a graded manner in Xenopus embryo and accumulated on the cell surface in a punctate manner in association with “N-sulfo-rich heparan sulfate (HS),” not with “N-acetyl-rich HS”. These two types of HS are differentially clustered by attaching to different glypicans as core proteins. N-sulfo-rich HS is frequently internalized and associated with the signaling vesicle, known as the Frizzled/Wnt/LRP6 signalosome, in the presence of Wnt8. Conversely, N-acetyl-rich HS is rarely internalized and accumulates Frzb, a secreted Wnt antagonist. Upon interaction with Frzb, Wnt8 associates with N-acetyl-rich HS, suggesting that N-acetyl-rich HS supports Frzb-mediated antagonism by sequestering Wnt8 from N-sulfo-rich HS. Thus, these two types of HS clusters may constitute a cellular platform for the distribution and signaling of Wnt8.<br />Wnt proteins mediate embryonic development but how protein localization and patterning is regulated is unclear. Here, the authors show that distinct structures with different heparan sulfate modifications (‘N-sulfo-rich’ and ‘N-acetyl-rich’) regulate cellular localization and signal transduction of Wnt8 in Xenopus.
- Subjects :
- 0301 basic medicine
Frizzled
Embryo, Nonmammalian
Science
Xenopus
General Physics and Astronomy
Xenopus Proteins
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
chemistry.chemical_compound
Xenopus laevis
Glypicans
Animals
Humans
lcsh:Science
Glycosaminoglycans
Multidisciplinary
biology
Chemistry
Wnt signaling pathway
LRP6
General Chemistry
Heparan sulfate
biology.organism_classification
Embryonic stem cell
Recombinant Proteins
Cell biology
Wnt Proteins
030104 developmental biology
Frzb
lcsh:Q
Heparitin Sulfate
Signal transduction
HeLa Cells
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....c2ad871bc6e20a309d23e18c211cf7ee