2020 Volume 32 Issue 190 Pages J181-J187
As a family of secreted signaling proteins, Wnt contributes to carcinogenesis, stem cell regulation, and various developmental processes in metazoans. Although Wnt has been considered as a morphogen that provides positional information via its concentration gradient, mechanisms by which Wnt proteins disperse in tissues are not fully understood. Heparan sulfate proteoglycans (HSPGs) are involved in distribution and signaling of secreted signaling proteins, including Wnt. Recently we found that HSPGs in Xenopus embryos and HeLa cells form clusters having different degrees of N-sulfation, which we refer to as “HS clusters.” HS clusters are generated from glypicans and modified by N-deacetylase/N-sulfotransferase in Xenopus embryos. They can be classified into N-acetyl-rich and N-sulfo-rich clusters. Importantly, N-sulfo-rich HS clusters may function as scaffolds for endogenous Wnt8, required for both its distribution and signaling. In this review, biological roles of Wnt signaling in embryogenesis and regulation of Wnt distribution and signaling by HSPGs are introduced together with our discovery of HS clusters.
