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Citation
Palm, W., Swierczynska, M.M., Kumari, V., Ehrhart-Bornstein, M., Bornstein, S.R., Eaton, S. (2013). Secretion and signaling activities of lipoprotein-associated hedgehog and non-sterol-modified hedgehog in flies and mammals.  PLoS Biol. 11(3): e1001505.
FlyBase ID
FBrf0221161
Publication Type
Research paper
Abstract

Hedgehog (Hh) proteins control animal development and tissue homeostasis. They activate gene expression by regulating processing, stability, and activation of Gli/Cubitus interruptus (Ci) transcription factors. Hh proteins are secreted and spread through tissue, despite becoming covalently linked to sterol during processing. Multiple mechanisms have been proposed to release Hh proteins in distinct forms; in Drosophila, lipoproteins facilitate long-range Hh mobilization but also contain lipids that repress the pathway. Here, we show that mammalian lipoproteins have conserved roles in Sonic Hedgehog (Shh) release and pathway repression. We demonstrate that lipoprotein-associated forms of Hh and Shh specifically block lipoprotein-mediated pathway inhibition. We also identify a second conserved release form that is not sterol-modified and can be released independently of lipoproteins (Hh-N*/Shh-N*). Lipoprotein-associated Hh/Shh and Hh-N*/Shh-N* have complementary and synergistic functions. In Drosophila wing imaginal discs, lipoprotein-associated Hh increases the amount of full-length Ci, but is insufficient for target gene activation. However, small amounts of non-sterol-modified Hh synergize with lipoprotein-associated Hh to fully activate the pathway and allow target gene expression. The existence of Hh secretion forms with distinct signaling activities suggests a novel mechanism for generating a diversity of Hh responses.

PubMed ID
PubMed Central ID
PMC3595218 (PMC) (EuropePMC)
Related Publication(s)
Note

Cholesterol-free and cholesterol-bound Hedgehog: Two sparring-partners working hand in hand in the Drosophila wing disc?
Ducuing and Querenet, 2013, Fly 7(4): 213--215 [FBrf0225114]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS Biol.
    Title
    PLoS Biology
    Publication Year
    2003-
    ISBN/ISSN
    1545-7885 1544-9173
    Data From Reference
    Genes (15)