The full-length unprocessed hedgehog protein is an active signaling molecule

Robert Tokhunts, Samer Singh, Tehyen Chu, Gisela D'Angelo, Valerie Baubet, John A. Goetz, Zhen Huang, Ziqiang Yuan, Manuel Ascano, Yana Zavros, Pascal P. Thérond, Sam Kunes, Nadia Dahmane, David J Robbins

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The hedgehog (HH) family of ligands plays an important instructional role in metazoan development. HH proteins are initially produced as -45-kDa full-length proteins, which undergo an intramolecular cleavage to generate an amino-terminal product that subsequently becomes cholesterol-modified (HH-Np). It is well accepted that this cholesterol-modified amino-terminal cleavage product is responsible for all HH-dependent signaling events. Contrary to this model we show here that full-length forms ofHHproteins are able to traffic to the plasma membrane and participate directly in cell-cell signaling, both in vitro and in vivo. We were also able to rescue a Drosophila eye-specific hh loss of function phenotype by expressing a full-length form of hh that cannot be processed into HH-Np. These results suggest that in some physiological contexts full-length HH proteins may participate directly in HH signaling and that this novel activity of full-length HH may be evolutionarily conserved.

Original languageEnglish
Pages (from-to)2562-2568
Number of pages7
JournalJournal of Biological Chemistry
Volume285
Issue number4
DOIs
StatePublished - Jan 22 2010
Externally publishedYes

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Hedgehog Proteins
Hedgehogs
Cholesterol
Cell signaling
Molecules
Cell membranes
Ligands
Proteins
Drosophila
Cell Membrane
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

The full-length unprocessed hedgehog protein is an active signaling molecule. / Tokhunts, Robert; Singh, Samer; Chu, Tehyen; D'Angelo, Gisela; Baubet, Valerie; Goetz, John A.; Huang, Zhen; Yuan, Ziqiang; Ascano, Manuel; Zavros, Yana; Thérond, Pascal P.; Kunes, Sam; Dahmane, Nadia; Robbins, David J.

In: Journal of Biological Chemistry, Vol. 285, No. 4, 22.01.2010, p. 2562-2568.

Research output: Contribution to journalArticle

Tokhunts, R, Singh, S, Chu, T, D'Angelo, G, Baubet, V, Goetz, JA, Huang, Z, Yuan, Z, Ascano, M, Zavros, Y, Thérond, PP, Kunes, S, Dahmane, N & Robbins, DJ 2010, 'The full-length unprocessed hedgehog protein is an active signaling molecule', Journal of Biological Chemistry, vol. 285, no. 4, pp. 2562-2568. https://doi.org/10.1074/jbc.M109.078626
Tokhunts R, Singh S, Chu T, D'Angelo G, Baubet V, Goetz JA et al. The full-length unprocessed hedgehog protein is an active signaling molecule. Journal of Biological Chemistry. 2010 Jan 22;285(4):2562-2568. https://doi.org/10.1074/jbc.M109.078626
Tokhunts, Robert ; Singh, Samer ; Chu, Tehyen ; D'Angelo, Gisela ; Baubet, Valerie ; Goetz, John A. ; Huang, Zhen ; Yuan, Ziqiang ; Ascano, Manuel ; Zavros, Yana ; Thérond, Pascal P. ; Kunes, Sam ; Dahmane, Nadia ; Robbins, David J. / The full-length unprocessed hedgehog protein is an active signaling molecule. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 4. pp. 2562-2568.
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