The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking

Karel F. Liem, Alyson Ashe, Mu He, Peter Satir, Jennifer Moran, David Beier, Carol Wicking, Kathryn V. Anderson

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Two intraflagellar transport (IFT) complexes, IFT-A and IFT-B, build and maintain primary cilia and are required for activity of the Sonic hedgehog (Shh) pathway. A weak allele of the IFT-A gene, Ift144, caused subtle defects in cilia structure and ectopic activation of the Shh pathway. In contrast, strong loss of IFT-A, caused by either absence of Ift144 or mutations in two IFT-A genes, blocked normal ciliogenesis and decreased Shh signaling. In strong IFT-A mutants, the Shh pathway proteins Gli2, Sufu, and Kif7 localized correctly to cilia tips, suggesting that these pathway components were trafficked by IFT-B. In contrast, the membrane proteins Arl13b, ACIII, and Smo failed to localize to primary cilia in the absence of IFT-A. We propose that the increased Shh activity seen in partial loss-of-function IFT-A mutants may be a result of decreased ciliary ACIII and that the loss of Shh activity in the absence of IFT-A is a result of severe disruptions of cilia structure and membrane protein trafficking.

Original languageEnglish (US)
Pages (from-to)789-800
Number of pages12
JournalJournal of Cell Biology
Volume197
Issue number6
DOIs
StatePublished - Jun 11 2012

ASJC Scopus subject areas

  • Cell Biology

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    Liem, K. F., Ashe, A., He, M., Satir, P., Moran, J., Beier, D., Wicking, C., & Anderson, K. V. (2012). The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking. Journal of Cell Biology, 197(6), 789-800. https://doi.org/10.1083/jcb.201110049