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Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium

Intracellular transduction of Hedgehog (Hh) signals in mammals requires functional primary cilia. The Hh signaling effectors, the Gli family of transcription factors, and their negative regulator, Suppressor of Fused (Sufu), accumulate at the tips of cilia; however, the molecular mechanism regulatin...

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Autores principales: Zeng, Huiqing, Jia, Jinping, Liu, Aimin
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012114/
https://www.ncbi.nlm.nih.gov/pubmed/21209912
http://dx.doi.org/10.1371/journal.pone.0015900
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author Zeng, Huiqing
Jia, Jinping
Liu, Aimin
author_facet Zeng, Huiqing
Jia, Jinping
Liu, Aimin
author_sort Zeng, Huiqing
collection PubMed
description Intracellular transduction of Hedgehog (Hh) signals in mammals requires functional primary cilia. The Hh signaling effectors, the Gli family of transcription factors, and their negative regulator, Suppressor of Fused (Sufu), accumulate at the tips of cilia; however, the molecular mechanism regulating this localization remains elusive. In the current study, we show that the ciliary localization of mammalian Gli proteins depends on both their N-terminal domains and a central region lying C-terminal to the zinc-finger DNA-binding domains. Invertebrate Gli homologs Ci and Tra1, when over-expressed in ciliated mouse fibroblasts, fail to localize to the cilia, suggesting the lack of a vertebrate-specific structural feature required for ciliary localization. We further show that activation of protein kinase A (PKA) efficiently inhibits ciliary localization of Gli2 and Gli3, but only moderately affects the ciliary localization of Gli1. Interestingly, variants of Gli2 mimicking the phosphorylated or non-phosphorylated states of Gli2 are both localized to the cilia, and their ciliary localizations are subjected to the inhibitory effect of PKA activation, suggesting a likely indirect mechanism underlying the roles of PKA in Gli ciliary localization. Finally, we show that ciliary localization of Sufu is dependent on ciliary-localized Gli proteins, and is inhibited by PKA activation, suggesting a coordinated mechanism for the ciliary translocation of Sufu and Gli proteins.
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spelling pubmed-30121142011-01-05 Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium Zeng, Huiqing Jia, Jinping Liu, Aimin PLoS One Research Article Intracellular transduction of Hedgehog (Hh) signals in mammals requires functional primary cilia. The Hh signaling effectors, the Gli family of transcription factors, and their negative regulator, Suppressor of Fused (Sufu), accumulate at the tips of cilia; however, the molecular mechanism regulating this localization remains elusive. In the current study, we show that the ciliary localization of mammalian Gli proteins depends on both their N-terminal domains and a central region lying C-terminal to the zinc-finger DNA-binding domains. Invertebrate Gli homologs Ci and Tra1, when over-expressed in ciliated mouse fibroblasts, fail to localize to the cilia, suggesting the lack of a vertebrate-specific structural feature required for ciliary localization. We further show that activation of protein kinase A (PKA) efficiently inhibits ciliary localization of Gli2 and Gli3, but only moderately affects the ciliary localization of Gli1. Interestingly, variants of Gli2 mimicking the phosphorylated or non-phosphorylated states of Gli2 are both localized to the cilia, and their ciliary localizations are subjected to the inhibitory effect of PKA activation, suggesting a likely indirect mechanism underlying the roles of PKA in Gli ciliary localization. Finally, we show that ciliary localization of Sufu is dependent on ciliary-localized Gli proteins, and is inhibited by PKA activation, suggesting a coordinated mechanism for the ciliary translocation of Sufu and Gli proteins. Public Library of Science 2010-12-29 /pmc/articles/PMC3012114/ /pubmed/21209912 http://dx.doi.org/10.1371/journal.pone.0015900 Text en Zeng et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zeng, Huiqing
Jia, Jinping
Liu, Aimin
Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium
title Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium
title_full Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium
title_fullStr Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium
title_full_unstemmed Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium
title_short Coordinated Translocation of Mammalian Gli Proteins and Suppressor of Fused to the Primary Cilium
title_sort coordinated translocation of mammalian gli proteins and suppressor of fused to the primary cilium
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012114/
https://www.ncbi.nlm.nih.gov/pubmed/21209912
http://dx.doi.org/10.1371/journal.pone.0015900
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