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Nat Commun 2017 Dec 07;81:1973. doi: 10.1038/s41467-017-02076-0.
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Roles of two types of heparan sulfate clusters in Wnt distribution and signaling in Xenopus.

Mii Y , Yamamoto T , Takada R , Mizumoto S , Matsuyama M , Yamada S , Takada S , Taira M .

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.

PubMed ID: 29215008
PMC ID: PMC5719454
Article link: Nat Commun

Species referenced: Xenopus laevis
Genes referenced: ctnnb1 frzb frzb2 fzd8 galnt3 gbx2.2 gpc4 gpc5 gpi gypc ighx lrp6 myc ndst1 spint1 sult2a1 wnt11 wnt3a wnt5a wnt8a
Morpholinos: fzd8 MO2 fzd8 MO3 gpc4 MO1 gpc4 MO5 gpc5 MO1 gpc5 MO2 ndst1 MO1 ndst1 MO2 wnt8a MO3 wnt8a MO7

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References [+] :
Ai, QSulf1 remodels the 6-O sulfation states of cell surface heparan sulfate proteoglycans to promote Wnt signaling. 2003, Pubmed