| Structural highlights
Function
[IHOG_DROME] Mediates response to the active Hedgehog (Hh) protein signal in embryos, functioning upstream or at the level of patched (ptc).[1] [HH_DROME] Intercellular signal essential for a variety of patterning events during development. Establishes the anterior-posterior axis of the embryonic segments and patterns the larval imaginal disks. Binds to the patched (ptc) receptor, which functions in association with smoothened (smo), to activate the transcription of target genes wingless (wg), decapentaplegic (dpp) and ptc. In the absence of hh, ptc represses the constitutive signaling activity of smo through fused (fu).[2] [3] [4] [5] The hedgehog protein N-product constitutes the active species in both local and long-range signaling, whereas the C-terminal product has no signaling activity. It acts as a morphogen, and diffuses long distances despite its lipidation. Heparan sulfate proteoglycans of the extracellular matrix play an essential role in diffusion. Lipophorin is required for diffusion, probably by acting as vehicle for its movement, explaining how it can spread over long distances despite its lipidation.[6] [7] [8] [9] The hedgehog protein C-product, which mediates the autocatalytic activity, has no signaling activity.[10] [11] [12] [13]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Hedgehog (Hh) signaling molecules mediate key tissue-patterning events during animal development, and inappropriate activation of Hh signaling in adults has been associated with human cancers. Recently, a conserved family of type I integral membrane proteins required for normal response to the Hh signal was discovered. One member of this family, Ihog (interference hedgehog), functions upstream or at the level of Patched (Ptc), but how Ihog participates in Hh signaling remains unclear. Here, we show that heparin binding induces Ihog dimerization and is required to mediate high-affinity interactions between Ihog and Hh. We also present crystal structures of a Hh-binding fragment of Ihog, both alone and complexed with Hh. Heparin is not well ordered in these structures, but a basic cleft in the first FNIII domain of Ihog (IhogFn1) is shown by mutagenesis to mediate heparin binding. These results establish that Hh directly binds Ihog and provide the first demonstration of a specific role for heparin in Hh responsiveness.
Structure of a heparin-dependent complex of Hedgehog and Ihog.,McLellan JS, Yao S, Zheng X, Geisbrecht BV, Ghirlando R, Beachy PA, Leahy DJ Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17208-13. Epub 2006 Oct 31. PMID:17077139[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yao S, Lum L, Beachy P. The ihog cell-surface proteins bind Hedgehog and mediate pathway activation. Cell. 2006 Apr 21;125(2):343-57. PMID:16630821 doi:http://dx.doi.org/10.1016/j.cell.2006.02.040
- ↑ Tashiro S, Michiue T, Higashijima S, Zenno S, Ishimaru S, Takahashi F, Orihara M, Kojima T, Saigo K. Structure and expression of hedgehog, a Drosophila segment-polarity gene required for cell-cell communication. Gene. 1993 Feb 28;124(2):183-9. PMID:8166882
- ↑ Lee JJ, von Kessler DP, Parks S, Beachy PA. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell. 1992 Oct 2;71(1):33-50. PMID:1394430
- ↑ Tabata T, Eaton S, Kornberg TB. The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. Genes Dev. 1992 Dec;6(12B):2635-45. PMID:1340474
- ↑ Lee JD, Kraus P, Gaiano N, Nery S, Kohtz J, Fishell G, Loomis CA, Treisman JE. An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development. Dev Biol. 2001 May 1;233(1):122-36. PMID:11319862 doi:http://dx.doi.org/10.1006/dbio.2001.0218
- ↑ Tashiro S, Michiue T, Higashijima S, Zenno S, Ishimaru S, Takahashi F, Orihara M, Kojima T, Saigo K. Structure and expression of hedgehog, a Drosophila segment-polarity gene required for cell-cell communication. Gene. 1993 Feb 28;124(2):183-9. PMID:8166882
- ↑ Lee JJ, von Kessler DP, Parks S, Beachy PA. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell. 1992 Oct 2;71(1):33-50. PMID:1394430
- ↑ Tabata T, Eaton S, Kornberg TB. The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. Genes Dev. 1992 Dec;6(12B):2635-45. PMID:1340474
- ↑ Lee JD, Kraus P, Gaiano N, Nery S, Kohtz J, Fishell G, Loomis CA, Treisman JE. An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development. Dev Biol. 2001 May 1;233(1):122-36. PMID:11319862 doi:http://dx.doi.org/10.1006/dbio.2001.0218
- ↑ Tashiro S, Michiue T, Higashijima S, Zenno S, Ishimaru S, Takahashi F, Orihara M, Kojima T, Saigo K. Structure and expression of hedgehog, a Drosophila segment-polarity gene required for cell-cell communication. Gene. 1993 Feb 28;124(2):183-9. PMID:8166882
- ↑ Lee JJ, von Kessler DP, Parks S, Beachy PA. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene hedgehog. Cell. 1992 Oct 2;71(1):33-50. PMID:1394430
- ↑ Tabata T, Eaton S, Kornberg TB. The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation. Genes Dev. 1992 Dec;6(12B):2635-45. PMID:1340474
- ↑ Lee JD, Kraus P, Gaiano N, Nery S, Kohtz J, Fishell G, Loomis CA, Treisman JE. An acylatable residue of Hedgehog is differentially required in Drosophila and mouse limb development. Dev Biol. 2001 May 1;233(1):122-36. PMID:11319862 doi:http://dx.doi.org/10.1006/dbio.2001.0218
- ↑ McLellan JS, Yao S, Zheng X, Geisbrecht BV, Ghirlando R, Beachy PA, Leahy DJ. Structure of a heparin-dependent complex of Hedgehog and Ihog. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17208-13. Epub 2006 Oct 31. PMID:17077139
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