Reference - Detail
|Author||Balmer S, Dussert A, Collu GM, Benitez E, Iomini C, Mlodzik M.|
|Title||Components of Intraflagellar Transport Complex A Function Independently of the Cilium to Regulate Canonical Wnt Signaling in Drosophila.|
The development of multicellular organisms requires the precisely coordinated regulation of an evolutionarily conserved group of signaling pathways. Temporal and spatial control of these signaling cascades is achieved through networks of regulatory proteins, segregation of pathway components in specific subcellular compartments, or both. In vertebrates, dysregulation of primary cilia function has been strongly linked to developmental signaling defects, yet it remains unclear whether cilia sequester pathway components to regulate their activation or cilia-associated proteins directly modulate developmental signaling events. To elucidate this question, we conducted an RNAi-based screen in Drosophila non-ciliated cells to test for cilium-independent loss-of-function phenotypes of ciliary proteins in developmental signaling pathways. Our results show no effect on Hedgehog signaling. In contrast, our screen identified several cilia-associated proteins as functioning in canonical Wnt signaling. Further characterization of specific components of Intraflagellar Transport complex A uncovered a cilia-independent function in potentiating Wnt signals by promoting β-catenin/Armadillo activity.
|MeSH||Animals Armadillo Domain Proteins / genetics Armadillo Domain Proteins / metabolism* Cells, Cultured Cilia / physiology* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism* Flagella / physiology* Hedgehog Proteins / genetics Hedgehog Proteins / metabolism Immunoenzyme Techniques Intracellular Signaling Peptides and Proteins / antagonists & inhibitors Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Multiprotein Complexes / antagonists & inhibitors Multiprotein Complexes / genetics Multiprotein Complexes / metabolism* RNA, Small Interfering / genetics Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism* Wnt Proteins / genetics Wnt Proteins / metabolism* beta Catenin / genetics beta Catenin / metabolism|
|WOS Category||DEVELOPMENTAL BIOLOGY CELL BIOLOGY|