title: Septate-junction-dependent luminal deposition of chitin deacetylases restricts tube elongation in the Drosophila trachea.
abstract: The function of tubular epithelial organs like the kidney and lung is critically dependent on the length and diameter of their constituting branches. Genetic analysis of tube size control during Drosophila tracheal development has revealed that epithelial septate junction (SJ) components and the dynamic chitinous luminal matrix coordinate tube growth. However, the underlying molecular mechanisms controlling tube expansion so far remained elusive. Here, we present the analysis of two luminal chitin binding proteins with predicted polysaccharide deacetylase activities (ChLDs). ChLDs are required to assemble the cable-like extracellular matrix (ECM) and restrict tracheal tube elongation. Overexpression of native, but not of mutated, ChLD versions also interferes with the structural integrity of the intraluminal ECM and causes aberrant tube elongation. Whereas ChLD mutants have normal SJ structure and function, the luminal deposition of the ChLD requires intact cellular SJs. This identifies a new molecular function for SJs in the apical secretion of ChLD and positions ChLD downstream of the SJs in tube length control. The deposition of the chitin luminal matrix first promotes and coordinates radial tube expansion. We propose that the subsequent structural modification of chitin by chitin binding deacetylases selectively instructs the termination of tube elongation to the underlying epithelium.
authors.affiliation: Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, Arrhenius Labs E3, S-10691 Stockholm, Sweden.
authors.forename: Shenqiu
authors.initials: S
authors.lastname: Wang
authors.forename: Satish Arcot
authors.initials: SA
authors.lastname: Jayaram
authors.forename: Johanna
authors.initials: J
authors.lastname: Hemphälä
authors.forename: Kirsten-André
authors.initials: KA
authors.lastname: Senti
authors.forename: Vasilios
authors.initials: V
authors.lastname: Tsarouhas
authors.forename: Haining
authors.initials: H
authors.lastname: Jin
authors.forename: Christos
authors.initials: C
authors.lastname: Samakovlis
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D048430:Cell Shape; D004330:Drosophila / Q000196:embryology* / Q000201:enzymology*; D029721:Drosophila Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000201:enzymology / Q000648:ultrastructure; D007365:Intercellular Junctions / Q000201:enzymology*; D009024:Morphogenesis; D010641:Phenotype; D014132:Trachea / Q000166:cytology / Q000196:embryology*
chemical_list: D029721:Drosophila Proteins; D000581:Amidohydrolases; C019866:chitin deacetylase