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SHh activity and localization is regulated by perlecan.
- Source :
-
Biological research [Biol Res] 2011; Vol. 44 (1), pp. 63-7. Date of Electronic Publication: 2011 May 11. - Publication Year :
- 2011
-
Abstract
- Proliferation and cell fate determination in the developing embryo are extrinsically regulated by multiple interactions among diverse secreted factors, such as Sonic Hedgehog (SHh), which act in a concentration-dependent manner. The fact that SHh is secreted as a lipid-modified protein suggests the existence of a mechanism to regulate its movement across embryonic fields. We have previously shown that heparan sulfate proteoglycans (HSPGs) are required for SHh binding and signalling. However, it was not determined which specific HSPG was responsible for these functions. Here we evaluated the contribution of perlecan on SHh localization and activity. To understand the mechanism of action of perlecan at the cellular level, we studied the role of perlecan-SHh interaction in SHh activity using both cell culture and biochemical assays. Our findings show that perlecan is a crucial anchor and modulator of SHh activity acting as an extracellular positive regulator of SHh.
- Subjects :
- Animals
Brain metabolism
Chromatography, Gel
Fibroblasts drug effects
Fibroblasts metabolism
Gene Expression Regulation, Developmental
Hedgehog Proteins metabolism
Heparan Sulfate Proteoglycans isolation & purification
Heparan Sulfate Proteoglycans metabolism
Heparan Sulfate Proteoglycans physiology
Humans
Immunohistochemistry
Mice
Rats
Brain drug effects
Heparan Sulfate Proteoglycans pharmacology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0717-6287
- Volume :
- 44
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Biological research
- Publication Type :
- Academic Journal
- Accession number :
- 21720682
- Full Text :
- https://doi.org/10.4067/S0716-97602011000100008