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Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling

The GPCR-family protein Smoothened (Smo) is essential for Hedgehog (Hh) signal transduction in both insects and vertebrates. The regulation of subcellular localization and abundance of Smo is a critical step in Hh signaling. Recent studies have demonstrated that Smo is subjected to ubiquitination me...

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Autores principales: Jia, Jianhang, Jiang, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936432/
https://www.ncbi.nlm.nih.gov/pubmed/35321245
http://dx.doi.org/10.3389/fcell.2022.847844
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author Jia, Jianhang
Jiang, Jin
author_facet Jia, Jianhang
Jiang, Jin
author_sort Jia, Jianhang
collection PubMed
description The GPCR-family protein Smoothened (Smo) is essential for Hedgehog (Hh) signal transduction in both insects and vertebrates. The regulation of subcellular localization and abundance of Smo is a critical step in Hh signaling. Recent studies have demonstrated that Smo is subjected to ubiquitination mediated by multiple E3 ubiquitin ligases, leading to Smo endocytosis and subsequent degradation through the proteasome- and lysosome-mediated pathways in Drosophila. Ubiquitination of Smo also promotes its ciliary exit in mammalian cells. Hh inhibits Smo ubiquitination by blocking E3 ligase recruitment and promoting Smo deubiquitination through the ubiquitin-specific protease 8 (USP8) in Drosophila. Inhibition of Smo ubiquitination by Hh promotes Smo cell surface accumulation in Drosophila and ciliary accumulation in mammalian cells. Interestingly, Hh also induces sumoylation of Smo in both Drosophila and mammalian cells, which promotes Smo cell surface/ciliary accumulation. This review focuses on how ubiquitination and sumoylation regulate Smo intracellular trafficking and abundance and how these processes are regulated by Hh.
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spelling pubmed-89364322022-03-22 Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling Jia, Jianhang Jiang, Jin Front Cell Dev Biol Cell and Developmental Biology The GPCR-family protein Smoothened (Smo) is essential for Hedgehog (Hh) signal transduction in both insects and vertebrates. The regulation of subcellular localization and abundance of Smo is a critical step in Hh signaling. Recent studies have demonstrated that Smo is subjected to ubiquitination mediated by multiple E3 ubiquitin ligases, leading to Smo endocytosis and subsequent degradation through the proteasome- and lysosome-mediated pathways in Drosophila. Ubiquitination of Smo also promotes its ciliary exit in mammalian cells. Hh inhibits Smo ubiquitination by blocking E3 ligase recruitment and promoting Smo deubiquitination through the ubiquitin-specific protease 8 (USP8) in Drosophila. Inhibition of Smo ubiquitination by Hh promotes Smo cell surface accumulation in Drosophila and ciliary accumulation in mammalian cells. Interestingly, Hh also induces sumoylation of Smo in both Drosophila and mammalian cells, which promotes Smo cell surface/ciliary accumulation. This review focuses on how ubiquitination and sumoylation regulate Smo intracellular trafficking and abundance and how these processes are regulated by Hh. Frontiers Media S.A. 2022-03-07 /pmc/articles/PMC8936432/ /pubmed/35321245 http://dx.doi.org/10.3389/fcell.2022.847844 Text en Copyright © 2022 Jia and Jiang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Jia, Jianhang
Jiang, Jin
Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling
title Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling
title_full Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling
title_fullStr Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling
title_full_unstemmed Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling
title_short Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling
title_sort regulation of smoothened trafficking and abundance in hedgehog signaling
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936432/
https://www.ncbi.nlm.nih.gov/pubmed/35321245
http://dx.doi.org/10.3389/fcell.2022.847844
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