Heparan sulfate proteoglycans exert positive and negative effects in Shh activity.
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.
Carrasco
Héctor
H
Department of Cell and Molecular Biology, Center for Cell Regulation and Pathology, Millennium Nucleus in Developmental Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile.
Olivares
Gonzalo H
GH
Faunes
Fernando
F
Oliva
Carlos
C
Larraín
Juan
J
D000595:Amino Acid Sequence; D000818:Animals; D002704:Chlorates / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D053823:Hedgehog Proteins; D019812:Heparan Sulfate Proteoglycans / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013431:Sulfates / Q000494:pharmacology; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
D002704:Chlorates; D053823:Hedgehog Proteins; D019812:Heparan Sulfate Proteoglycans; D010455:Peptides; D013431:Sulfates; D015534:Trans-Activators