title: Wurst is essential for airway clearance and respiratory-tube size control.
abstract: The Drosophila melanogaster tracheal system and the mammalian lung are branching networks of tubular epithelia that convert during late embryogenesis from liquid- to air-filling. Little is known about how respiratory-tube size and physiology are coordinated. Here, we show that the Drosophila wurst gene encodes a unique J-domain transmembrane protein highly conserved in metazoa. In wurst mutants, respiratory-tube length is increased and lumen clearance is abolished, preventing gas filling of the airways. Wurst is essential for clathrin-mediated endocytosis, which is required for size determination and lumen clearance of the airways. wurst recruits heat shock cognate protein 70-4 and clathrin to the apical membrane of epithelial cells. The sequence conservation of the single Wurst orthologues in mice and humans offer new opportunities for genetic studies of clinically relevant lung syndromes caused by the failure of liquid clearance and respiratory-tube size control.
authors.affiliation: LIMES-Institute, Program Unit Development & Genetics, Laboratory for Molecular Developmental Biology, University of Bonn, Meckenheimer Allee 169, D-53115 Bonn, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Behr
authors.forename: Christian
authors.initials: C
authors.lastname: Wingen
authors.forename: Christian
authors.initials: C
authors.lastname: Wolf
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schuh
authors.forename: Michael
authors.initials: M
authors.lastname: Hoch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016764:Cell Polarity; D002966:Clathrin / Q000378:metabolism; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology*; D004705:Endocytosis; D004847:Epithelial Cells / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009024:Morphogenesis; D010802:Phylogeny; D011485:Protein Binding; D012137:Respiratory System; D014132:Trachea / Q000033:anatomy & histology / Q000196:embryology
chemical_list: D002966:Clathrin; D029721:Drosophila Proteins; D050883:HSC70 Heat-Shock Proteins; D008565:Membrane Proteins; C522279:wus protein, Drosophila