The IFT-A Complex Regulates Shh Signaling through Cilia Structure and Membrane Protein Trafficking
Liem, Karel F., Jr.
Anderson, Kathryn V.
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CitationLiem, Karel F., Jr., Alyson Ashe, Mu He, Peter Satir, Jennifer Moran, David Randolph Beier, Carol Wicking, and Kathryn V. Anderson. 2012. The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking. The Journal of Cell Biology 197(6): 789-800.
AbstractTwo 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.
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