Research ArticleCell Biology

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

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Science Signaling  09 Dec 2014:
Vol. 7, Issue 355, pp. ra117
DOI: 10.1126/scisignal.2005608

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Dephosphorylation for Hedgehog Signaling

Signaling through the developmentally important Hedgehog pathway requires the primary cilium. Localization of components of the Hedgehog pathway determines their activity. Kinesins are a family of motor proteins that traffic cargo along microtubules. Liu et al. found that liprin-α1 acted as a bridge between the protein phosphatase PP2A and the kinesin protein Kif7, which can either promote or attenuate Hedgehog signaling. Dephosphorylation of Kif7 enhanced its localization at the tips of cilia and stimulated Hedgehog signaling. A disease-associated mutation in the domain of Kif7 required for binding to liprin-α1 increased the association of Kif7 with the liprin-α1–PP2A complex. Overexpression of this mutant or a form of Kif7 that lacked the phosphorylation site induced Hedgehog signaling in a ligand-independent manner.

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