Ihog and Boi elicit Hh signaling via Ptc but do not aid Ptc in sequestering the Hh ligand
© 2014. Published by The Company of Biologists Ltd..
Hedgehog (Hh) proteins are secreted molecules essential for tissue development in vertebrates and invertebrates. Hh reception via the 12-pass transmembrane protein Patched (Ptc) elicits intracellular signaling through Smoothened (Smo). Hh binding to Ptc is also proposed to sequester the ligand, limiting its spatial range of activity. In Drosophila, Interference hedgehog (Ihog) and Brother of ihog (Boi) are two conserved and redundant transmembrane proteins that are essential for Hh pathway activation. How Ihog and Boi activate signaling in response to Hh remains unknown; each can bind both Hh and Ptc and so it has been proposed that they are essential for both Hh reception and sequestration. Using genetic epistasis we established here that Ihog and Boi, and their orthologs in mice, act upstream or at the level of Ptc to allow Hh signal transduction. In the Drosophila developing wing model we found that it is through Hh pathway activation that Ihog and Boi maintain the boundary between the anterior and posterior compartments. We dissociated the contributions of Ptc from those of Ihog/Boi and, surprisingly, found that cells expressing Ptc can retain and sequester the Hh ligand without Ihog and Boi, but that Ihog and Boi cannot do so without Ptc. Together, these results reinforce the central role for Ptc in Hh binding in vivo and demonstrate that, although Ihog and Boi are dispensable for Hh sequestration, they are essential for pathway activation because they allow Hh to inhibit Ptc and thereby relieve its repression of Smo.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:141 |
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| Enthalten in: |
Development (Cambridge, England) - 141(2014), 20 vom: 18. Okt., Seite 3879-88 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Camp, Darius [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.12.2014 Date Revised 21.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1242/dev.103564 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a Ihog and Boi elicit Hh signaling via Ptc but do not aid Ptc in sequestering the Hh ligand |
| 264 | 1 | |c 2014 | |
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| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2014. Published by The Company of Biologists Ltd. | ||
| 520 | |a Hedgehog (Hh) proteins are secreted molecules essential for tissue development in vertebrates and invertebrates. Hh reception via the 12-pass transmembrane protein Patched (Ptc) elicits intracellular signaling through Smoothened (Smo). Hh binding to Ptc is also proposed to sequester the ligand, limiting its spatial range of activity. In Drosophila, Interference hedgehog (Ihog) and Brother of ihog (Boi) are two conserved and redundant transmembrane proteins that are essential for Hh pathway activation. How Ihog and Boi activate signaling in response to Hh remains unknown; each can bind both Hh and Ptc and so it has been proposed that they are essential for both Hh reception and sequestration. Using genetic epistasis we established here that Ihog and Boi, and their orthologs in mice, act upstream or at the level of Ptc to allow Hh signal transduction. In the Drosophila developing wing model we found that it is through Hh pathway activation that Ihog and Boi maintain the boundary between the anterior and posterior compartments. We dissociated the contributions of Ptc from those of Ihog/Boi and, surprisingly, found that cells expressing Ptc can retain and sequester the Hh ligand without Ihog and Boi, but that Ihog and Boi cannot do so without Ptc. Together, these results reinforce the central role for Ptc in Hh binding in vivo and demonstrate that, although Ihog and Boi are dispensable for Hh sequestration, they are essential for pathway activation because they allow Hh to inhibit Ptc and thereby relieve its repression of Smo | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Drosophila | |
| 650 | 4 | |a Morphogenesis | |
| 650 | 4 | |a Pattern formation | |
| 650 | 4 | |a Signaling | |
| 650 | 7 | |a Boi protein, Drosophila |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Drosophila Proteins |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Membrane Glycoproteins |2 NLM | |
| 650 | 7 | |a Patched Receptors |2 NLM | |
| 650 | 7 | |a Patched-1 Receptor |2 NLM | |
| 650 | 7 | |a Ptch1 protein, mouse |2 NLM | |
| 650 | 7 | |a Receptors, Cell Surface |2 NLM | |
| 650 | 7 | |a iHog protein, Drosophila |2 NLM | |
| 650 | 7 | |a ptc protein, Drosophila |2 NLM | |
| 700 | 1 | |a Haitian He, Billy |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Sally |e verfasserin |4 aut | |
| 700 | 1 | |a Althaus, Irene W |e verfasserin |4 aut | |
| 700 | 1 | |a Holtz, Alexander M |e verfasserin |4 aut | |
| 700 | 1 | |a Allen, Benjamin L |e verfasserin |4 aut | |
| 700 | 1 | |a Charron, Frédéric |e verfasserin |4 aut | |
| 700 | 1 | |a van Meyel, Donald J |e verfasserin |4 aut | |
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