Cargando…

E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened

The Hedgehog pathway, critical to vertebrate development, is organized in primary cilia. Activation of signaling causes the Hedgehog receptor Ptch1 to exit cilia, allowing a second receptor, Smo, to accumulate in cilia and activate the downstream steps of the pathway. Mechanisms regulating the dynam...

Descripción completa

Detalles Bibliográficos
Autores principales: Lv, Bo, Stuck, Michael W., Desai, Paurav B., Cabrera, Oscar A., Pazour, Gregory J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236919/
https://www.ncbi.nlm.nih.gov/pubmed/34161574
http://dx.doi.org/10.1083/jcb.202010177
_version_ 1783714644192395264
author Lv, Bo
Stuck, Michael W.
Desai, Paurav B.
Cabrera, Oscar A.
Pazour, Gregory J.
author_facet Lv, Bo
Stuck, Michael W.
Desai, Paurav B.
Cabrera, Oscar A.
Pazour, Gregory J.
author_sort Lv, Bo
collection PubMed
description The Hedgehog pathway, critical to vertebrate development, is organized in primary cilia. Activation of signaling causes the Hedgehog receptor Ptch1 to exit cilia, allowing a second receptor, Smo, to accumulate in cilia and activate the downstream steps of the pathway. Mechanisms regulating the dynamics of these receptors are unknown, but the ubiquitination of Smo regulates its interaction with the intraflagellar transport system to control ciliary levels. A focused screen of ubiquitin-related genes identified nine required for maintaining low ciliary Smo at the basal state. These included cytoplasmic E3s (Arih2, Mgrn1, and Maea), a ciliary localized E3 (Wwp1), a ciliary localized E2 (Ube2l3), a deubiquitinase (Bap1), and three adaptors (Kctd5, Skp1a, and Skp2). The ciliary E3, Wwp1, binds Ptch1 and localizes to cilia at the basal state. Activation of signaling removes both Ptch1 and Wwp1 from cilia, thus providing an elegant mechanism for Ptch1 to regulate ciliary Smo levels.
format Online
Article
Text
id pubmed-8236919
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-82369192022-03-06 E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened Lv, Bo Stuck, Michael W. Desai, Paurav B. Cabrera, Oscar A. Pazour, Gregory J. J Cell Biol Article The Hedgehog pathway, critical to vertebrate development, is organized in primary cilia. Activation of signaling causes the Hedgehog receptor Ptch1 to exit cilia, allowing a second receptor, Smo, to accumulate in cilia and activate the downstream steps of the pathway. Mechanisms regulating the dynamics of these receptors are unknown, but the ubiquitination of Smo regulates its interaction with the intraflagellar transport system to control ciliary levels. A focused screen of ubiquitin-related genes identified nine required for maintaining low ciliary Smo at the basal state. These included cytoplasmic E3s (Arih2, Mgrn1, and Maea), a ciliary localized E3 (Wwp1), a ciliary localized E2 (Ube2l3), a deubiquitinase (Bap1), and three adaptors (Kctd5, Skp1a, and Skp2). The ciliary E3, Wwp1, binds Ptch1 and localizes to cilia at the basal state. Activation of signaling removes both Ptch1 and Wwp1 from cilia, thus providing an elegant mechanism for Ptch1 to regulate ciliary Smo levels. Rockefeller University Press 2021-06-23 /pmc/articles/PMC8236919/ /pubmed/34161574 http://dx.doi.org/10.1083/jcb.202010177 Text en © 2021 Lv et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Lv, Bo
Stuck, Michael W.
Desai, Paurav B.
Cabrera, Oscar A.
Pazour, Gregory J.
E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened
title E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened
title_full E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened
title_fullStr E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened
title_full_unstemmed E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened
title_short E3 ubiquitin ligase Wwp1 regulates ciliary dynamics of the Hedgehog receptor Smoothened
title_sort e3 ubiquitin ligase wwp1 regulates ciliary dynamics of the hedgehog receptor smoothened
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236919/
https://www.ncbi.nlm.nih.gov/pubmed/34161574
http://dx.doi.org/10.1083/jcb.202010177
work_keys_str_mv AT lvbo e3ubiquitinligasewwp1regulatesciliarydynamicsofthehedgehogreceptorsmoothened
AT stuckmichaelw e3ubiquitinligasewwp1regulatesciliarydynamicsofthehedgehogreceptorsmoothened
AT desaipauravb e3ubiquitinligasewwp1regulatesciliarydynamicsofthehedgehogreceptorsmoothened
AT cabreraoscara e3ubiquitinligasewwp1regulatesciliarydynamicsofthehedgehogreceptorsmoothened
AT pazourgregoryj e3ubiquitinligasewwp1regulatesciliarydynamicsofthehedgehogreceptorsmoothened