Intraflagellar Transport is Deeply Integrated in Hedgehog Signaling

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2018 Mar 16

PMID 29540531

Citations 28

Authors

Thibaut Eguether

Fabrice P Cordelieres

Gregory J Pazour

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Collaborative role of two distinct cilium-specific cytoskeletal systems in driving Hedgehog-responsive transcription factor trafficking.

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Alteration of primary cilia and intraflagellar transport 20 (IFT20) expression in oral squamous cell carcinoma (OSCC) cell lines.

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Structure and tethering mechanism of dynein-2 intermediate chains in intraflagellar transport.

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