title: The planar cell polarity effector Fuz is essential for targeted membrane trafficking, ciliogenesis and mouse embryonic development.
abstract: The planar cell polarity (PCP) signalling pathway is essential for embryonic development because it governs diverse cellular behaviours, and 'core PCP' proteins, such as Dishevelled and Frizzled, have been extensively characterized. By contrast, the 'PCP effector' proteins, such as Intu and Fuz, remain largely unstudied. These proteins are essential for PCP signalling, but they have never been investigated in mammals and their cell biological activities remain entirely unknown. We report here that Fuz mutant mice show neural tube defects, skeletal dysmorphologies and Hedgehog signalling defects stemming from disrupted ciliogenesis. Using bioinformatics and imaging of an in vivo mucociliary epithelium, we established a central role for Fuz in membrane trafficking, showing that Fuz is essential for trafficking of cargo to basal bodies and to the apical tips of cilia. Fuz is also essential for exocytosis in secretory cells. Finally, we identified a Rab-related small GTPase as a Fuz interaction partner that is also essential for ciliogenesis and secretion. These results are significant because they provide new insights into the mechanisms by which developmental regulatory systems such as PCP signalling interface with fundamental cellular systems such as the vesicle trafficking machinery.
authors.affiliation: Dept. of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas 78712, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Gray
authors.forename: Philip B
authors.initials: PB
authors.lastname: Abitua
authors.forename: Bogdan J
authors.initials: BJ
authors.lastname: Wlodarczyk
authors.forename: Heather L
authors.initials: HL
authors.lastname: Szabo-Rogers
authors.forename: Otis
authors.initials: O
authors.lastname: Blanchard
authors.forename: Insuk
authors.initials: I
authors.lastname: Lee
authors.forename: Greg S
authors.initials: GS
authors.lastname: Weiss
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Liu
authors.forename: Edward M
authors.initials: EM
authors.lastname: Marcotte
authors.forename: John B
authors.initials: JB
authors.lastname: Wallingford
authors.forename: Richard H
authors.initials: RH
authors.lastname: Finnell
mesh_terms: D000015:Abnormalities, Multiple; D000818:Animals; D016764:Cell Polarity / Q000235:genetics*; D002923:Cilia / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D003598:Cytoskeletal Proteins; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006720:Homozygote; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008958:Models, Molecular; D054259:Neural Tube / Q000002:abnormalities; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; C544812:Fuz protein, mouse; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins