Intraflagellar transport is deeply integrated in hedgehog signaling
MBoC. 2018-05-15; 29(10): 1178-1189
DOI: 10.1091/mbc.e17-10-0600
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1. Mol Biol Cell. 2018 May 15;29(10):1178-1189. doi: 10.1091/mbc.E17-10-0600. Epub
2018 Mar 22.
Intraflagellar transport is deeply integrated in hedgehog signaling.
Eguether T(1), Cordelieres FP(2), Pazour GJ(1).
Author information:
(1)Program in Molecular Medicine, University of Massachusetts Medical School,
Worcester, MA 01605.
(2)Université de Bordeaux, UMS 3420 CNRS-Université de Bordeaux-US4 INSERM,
Bordeaux Imaging Center, F-33000 Bordeaux, France.
The vertebrate hedgehog pathway is organized in primary cilia, and hedgehog
components relocate into or out of cilia during signaling. Defects in
intraflagellar transport (IFT) typically disrupt ciliary assembly and attenuate
hedgehog signaling. Determining whether IFT drives the movement of hedgehog
components is difficult due to the requirement of IFT for building cilia. Unlike
most IFT proteins, IFT27 is dispensable for cilia formation but affects hedgehog
signaling similarly to other IFTs, allowing us to examine its role in the
dynamics of signaling. Activating signaling at points along the pathway in Ift27
mutant cells showed that IFT is extensively involved in the pathway. Similar
analysis of Bbs mutant cells showed that BBS proteins participate at many levels
of signaling but are not needed to concentrate Gli transcription factors at the
ciliary tip. Our analysis showed that smoothened delivery to cilia does not
require IFT27, but the role of other IFTs is not known. Using a rapamycin-induced
dimerization system to sequester IFT-B proteins at the mitochondria in cells with
fully formed cilia did not affect the delivery of Smo to cilia, suggesting that
this membrane protein may not require IFT-B for delivery.
DOI: 10.1091/mbc.E17-10-0600
PMCID: PMC5935068
PMID: 29540531