Coordinated translocation of mammalian gli proteins and suppressor of fused to the primary cilium

Huiqing Zeng, Jinping Jia, Aimin Liu

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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 Cterminal 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.

Original languageEnglish (US)
Article numbere15900
JournalPLoS One
Volume5
Issue number12
DOIs
StatePublished - Dec 1 2010

Fingerprint

cAMP-dependent protein kinase
Cilia
cilia
Cyclic AMP-Dependent Protein Kinases
Hedgehogs
Erinaceidae
Chemical activation
Proteins
proteins
Mammals
zinc finger motif
Zinc Fingers
Invertebrates
Fibroblasts
fibroblasts
Vertebrates
Zinc
Signal Transduction
Transcription Factors
transcription factors

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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abstract = "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 Cterminal 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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Coordinated translocation of mammalian gli proteins and suppressor of fused to the primary cilium. / Zeng, Huiqing; Jia, Jinping; Liu, Aimin.

In: PLoS One, Vol. 5, No. 12, e15900, 01.12.2010.

Research output: Contribution to journalArticle

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