The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking Journal Article
| Authors: | Liem, K. F. Jr; Ashe, A.; He, M.; Satir, P.; Moran, J.; Beier, D.; Wicking, C.; Anderson, K. V. |
| Article Title: | The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking |
| 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. © 2012 Liem et al. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; protein localization; proteins; animal cell; mouse; animals; mice; microscopy, electron; allele; cell structure; embryo; sonic hedgehog protein; hedgehog proteins; membrane proteins; mice, inbred c57bl; intracellular signaling peptides and proteins; membrane protein; kruppel-like transcription factors; repressor proteins; loss of function mutation; erinaceidae; smoothened protein; eukaryotic flagellum; cilia; flagella; kinesin; aciii protein; arl13b protein; ift144 protein; intraflagellar transport a complex; intraflagellar transport b complex |
| Journal Title: | Journal of Cell Biology |
| Volume: | 197 |
| Issue: | 6 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2012-06-11 |
| Start Page: | 789 |
| End Page: | 800 |
| Language: | English |
| DOI: | 10.1083/jcb.201110049 |
| PROVIDER: | scopus |
| PMCID: | PMC3373400 |
| PUBMED: | 22689656 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 August 2012" - "CODEN: JCLBA" - "Source: Scopus" |
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