A study on the interactions between heparan sulfate proteoglycans and Wnt proteins.
The Wnt signaling pathway plays key roles in development and adult homeostasis. Wnt proteins are secreted, lipid-modified glycoproteins. They can form morphogen gradients that are regulated at the level of protein secretion, diffusion, and internalization. These gradients can only exist if the hydrophobic Wnt proteins are prevented from aggregating in the extracellular environment. Heparan sulfate proteoglycans (HSPGs) are necessary for proper activity of Wnt proteins and influence their distribution along the morphogenetic gradient. In this study, we show that HSPGs are able to maintain the solubility of Wnt proteins, thus stabilizing their signaling activity. Our results suggest that the role of HSPGs is not only to concentrate Wnt molecules at the cell surface but also to prevent them from aggregating in the extracellular environment.
Fuerer
Christophe
C
Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Habib
Shukry J
SJ
Nusse
Roel
R
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism* / Q000494:pharmacology; D008156:Luciferases; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012995:Solubility / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism*; D060508:Wnt3 Protein; D001616:beta-Galactosidase
D019812:Heparan Sulfate Proteoglycans; D051153:Wnt Proteins; D060508:Wnt3 Protein; D008156:Luciferases; D001616:beta-Galactosidase
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