title: Components of Intraflagellar Transport Complex A Function Independently of the Cilium to Regulate Canonical Wnt Signaling in Drosophila.
abstract: 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.
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Balmer
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Aurore
authors.initials: A
authors.lastname: Dussert
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Giovanna M
authors.initials: GM
authors.lastname: Collu
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Elvira
authors.initials: E
authors.lastname: Benitez
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Iomini
authors.affiliation: Department of Developmental & Regenerative Biology and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA. Electronic address: marek.mlodzik@mssm.edu.
authors.forename: Marek
authors.initials: M
authors.lastname: Mlodzik
mesh_terms: D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D005407:Flagella / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin