Heparan sulfate proteoglycans exert positive and negative effects in Shh activity

Héctor Carrasco, Gonzalo H. Olivares, Fernando Faunes, Carlos Oliva, Juan Larraín

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Hedgehog (Hh) proteins are morphogens involved in short-and long-range effects during early embryonic development. Genetic analysis in fly and vertebrate embryos showed that heparan sulfate proteoglycans (HSPGs) are required for Hh transport and signaling. To further understand how HSPGs regulate Sonic hedgehog (Shh), we performed experiments using cell culture and biochemical assays. When the synthesis of HSPGs was reduced, a decrease in Shh activity was observed. Contrary to that, addition of a peptide that competes the binding of Shh to HSPGs resulted in augmentation of Shh activity. From these results, we concluded that HSPGs exert positive and negative effects in Shh activity. This dual effect correlates with the finding that Shh interacts preferentially with two HSPGs. The current model for the role of HSPGs in Shh diffusion is discussed in view of our findings.

Original languageEnglish
Pages (from-to)831-838
Number of pages8
JournalJournal of Cellular Biochemistry
Volume96
Issue number4
DOIs
Publication statusPublished - 1 Nov 2005

Keywords

  • Morphogen gradients
  • Proteoglycans
  • Shh

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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