Hedgehog lipid modifications are required for Hedgehog stabilization in the extracellular matrix
| Autor: | Luis Quijada, Carlos Torroja, Isabel Guerrero, Ainhoa Callejo |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Recombinant Fusion Proteins
Cell Embryonic Structures Apical plasma membrane Biology Heparan Sulfate Proteoglycans Extracellular matrix Genes Reporter medicine Animals Drosophila Proteins Wings Animal Hedgehog Proteins Transgenes Molecular Biology Hedgehog Cell Membrane Wild type Membrane Proteins Lipids Cell biology Extracellular Matrix Imaginal disc medicine.anatomical_structure Drosophila melanogaster Biochemistry Function (biology) Developmental Biology Signal Transduction |
| Zdroj: | Development (Cambridge, England). 133(3) |
| ISSN: | 0950-1991 |
| Popis: | The Hedgehog (Hh) family of morphogenetic proteins has important instructional roles in metazoan development. Despite Hh being modified by Ct-cholesterol and Nt-palmitate adducts, Hh migrates far from its site of synthesis and programs cellular outcomes, depending on its local concentrations. We show that in the receiving cells of the Drosophilawing imaginal disc, lipid-unmodified Hh spreads across many more cell diameters than the wild type and this spreading leads to the activation of low but not high threshold responses. Unlipidated Hh forms become internalized through the apical plasma membrane, while wild-type Hh enters through the basolateral cell surface - in all cases via a dynamin-dependent mechanism. Full activation of the Hh pathway and the spread of Hh throughout the extracellular matrix depend on the ability of lipid-modified Hh to interact with heparan sulfate proteoglycans (HSPG). However, neither Hh-lipid modifications nor HSPG function are required to activate the targets that respond to low levels of Hh. All these data show that the interaction of lipid-modified Hh with HSPG is important both for precise Hh spreading through the epithelium surface and for correct Hh reception. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|