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Sci Signal. 2014 Dec 9;7(355):ra117. doi: 10.1126/scisignal.2005608.

The PPFIA1-PP2A protein complex promotes trafficking of Kif7 to the ciliary tip and Hedgehog signaling.

Author information

1
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
2
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
3
Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
4
Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Program in Developmental and Stem Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
5
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
6
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada. Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada. stephane.angers@utoronto.ca.

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.

PMID:
25492966
DOI:
10.1126/scisignal.2005608
[Indexed for MEDLINE]

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