PUBLICATION
The PPFIA1-PP2A protein complex promotes trafficking of Kif7 to the ciliary tip and Hedgehog signaling
- Authors
- Liu, Y.C., Couzens, A.L., Deshwar, A.R., B McBroom-Cerajewski, L.D., Zhang, X., Puviindran, V., Scott, I.C., Gingras, A.C., Hui, C.C., Angers, S.
- ID
- ZDB-PUB-170214-249
- Date
- 2014
- Source
- Science signaling 7: ra117 (Journal)
- Registered Authors
- Deshwar, Ashish, Scott, Ian
- Keywords
- none
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/genetics
- Adaptor Proteins, Signal Transducing/metabolism*
- Animals
- Cilia/genetics
- Cilia/metabolism
- HEK293 Cells
- Hedgehog Proteins/genetics
- Hedgehog Proteins/metabolism*
- Humans
- Kinesins/genetics
- Kinesins/metabolism*
- Kruppel-Like Transcription Factors/genetics
- Kruppel-Like Transcription Factors/metabolism
- Mice
- Protein Phosphatase 2/genetics
- Protein Phosphatase 2/metabolism*
- Proteins/genetics
- Proteins/metabolism*
- Signal Transduction/physiology*
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Transcription, Genetic/physiology
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Zinc Finger Protein GLI1
- PubMed
- 25492966 Full text @ Sci. Signal.
Citation
Liu, Y.C., Couzens, A.L., Deshwar, A.R., B McBroom-Cerajewski, L.D., Zhang, X., Puviindran, V., Scott, I.C., Gingras, A.C., Hui, C.C., Angers, S. (2014) The PPFIA1-PP2A protein complex promotes trafficking of Kif7 to the ciliary tip and Hedgehog signaling. Science signaling. 7:ra117.
Abstract
The primary cilium is required for Hedgehog (Hh) signaling in vertebrates. Hh leads to ciliary accumulation and activation of the transmembrane protein Smoothened (Smo) and affects the localization of several pathway components, including the Gli family of transcriptional regulators, within different regions of primary cilia. Genetic analysis indicates that the kinesin protein Kif7 both promotes and inhibits mouse Hh signaling. Using mass spectrometry, we identified liprin-α1 (PPFIA1) and the protein phosphatase PP2A as Kif7-interacting proteins, and we showed that they were important for the trafficking of Kif7 and Gli proteins to the tips of cilia and for the transcriptional output of Hh signaling. Our results suggested that PPFIA1 functioned with PP2A to promote the dephosphorylation of Kif7, triggering Kif7 localization to the tips of primary cilia and promoting Gli transcriptional activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping