High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened
The oncogenic G-protein-coupled receptor (GPCR) Smoothened (SMO) is a key transducer of the hedgehog (HH) morphogen, which plays an essential role in the patterning of epithelial structures. Here, we examine how HH controls SMO subcellular localization and activity in a polarized epithelium using th...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/79843 |
| _version_ | 1811252579570548736 |
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| author | Marina Gonçalves Antunes Matthieu Sanial Vincent Contremoulins Sandra Carvalho Anne Plessis Isabelle Becam |
| author_facet | Marina Gonçalves Antunes Matthieu Sanial Vincent Contremoulins Sandra Carvalho Anne Plessis Isabelle Becam |
| author_sort | Marina Gonçalves Antunes |
| collection | DOAJ |
| description | The oncogenic G-protein-coupled receptor (GPCR) Smoothened (SMO) is a key transducer of the hedgehog (HH) morphogen, which plays an essential role in the patterning of epithelial structures. Here, we examine how HH controls SMO subcellular localization and activity in a polarized epithelium using the Drosophila wing imaginal disc as a model. We provide evidence that HH promotes the stabilization of SMO by switching its fate after endocytosis toward recycling. This effect involves the sequential and additive action of protein kinase A, casein kinase I, and the Fused (FU) kinase. Moreover, in the presence of very high levels of HH, the second effect of FU leads to the local enrichment of SMO in the most basal domain of the cell membrane. Together, these results link the morphogenetic effects of HH to the apico-basal distribution of SMO and provide a novel mechanism for the regulation of a GPCR. |
| first_indexed | 2024-04-12T16:37:48Z |
| format | Article |
| id | doaj.art-a63dfa4266ec4e82b5c5ddb38962d0a0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:37:48Z |
| publishDate | 2022-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a63dfa4266ec4e82b5c5ddb38962d0a02022-12-22T03:24:56ZengeLife Sciences Publications LtdeLife2050-084X2022-09-011110.7554/eLife.79843High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothenedMarina Gonçalves Antunes0https://orcid.org/0000-0003-3818-4434Matthieu Sanial1https://orcid.org/0000-0002-0301-4710Vincent Contremoulins2Sandra Carvalho3https://orcid.org/0000-0002-8654-0539Anne Plessis4https://orcid.org/0000-0001-9193-7031Isabelle Becam5https://orcid.org/0000-0002-4464-7880Université Paris Cité, CNRS, Institut Jacques Monod, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, FranceUniversité Paris Cité, CNRS, Institut Jacques Monod, Paris, FranceThe oncogenic G-protein-coupled receptor (GPCR) Smoothened (SMO) is a key transducer of the hedgehog (HH) morphogen, which plays an essential role in the patterning of epithelial structures. Here, we examine how HH controls SMO subcellular localization and activity in a polarized epithelium using the Drosophila wing imaginal disc as a model. We provide evidence that HH promotes the stabilization of SMO by switching its fate after endocytosis toward recycling. This effect involves the sequential and additive action of protein kinase A, casein kinase I, and the Fused (FU) kinase. Moreover, in the presence of very high levels of HH, the second effect of FU leads to the local enrichment of SMO in the most basal domain of the cell membrane. Together, these results link the morphogenetic effects of HH to the apico-basal distribution of SMO and provide a novel mechanism for the regulation of a GPCR.https://elifesciences.org/articles/79843hedgehogsmoothenedDrosophilaapico-basal polarityprotein traffickingphosphorylation |
| spellingShingle | Marina Gonçalves Antunes Matthieu Sanial Vincent Contremoulins Sandra Carvalho Anne Plessis Isabelle Becam High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened eLife hedgehog smoothened Drosophila apico-basal polarity protein trafficking phosphorylation |
| title | High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened |
| title_full | High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened |
| title_fullStr | High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened |
| title_full_unstemmed | High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened |
| title_short | High hedgehog signaling is transduced by a multikinase-dependent switch controlling the apico-basal distribution of the GPCR smoothened |
| title_sort | high hedgehog signaling is transduced by a multikinase dependent switch controlling the apico basal distribution of the gpcr smoothened |
| topic | hedgehog smoothened Drosophila apico-basal polarity protein trafficking phosphorylation |
| url | https://elifesciences.org/articles/79843 |
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