title: Obstructor-A is required for epithelial extracellular matrix dynamics, exoskeleton function, and tubulogenesis.
abstract: The epidermis and internal tubular organs, such as gut and lungs, are exposed to a hostile environment. They form an extracellular matrix to provide epithelial integrity and to prevent contact with pathogens and toxins. In arthropods, the cuticle protects, shapes, and enables the functioning of organs. During development, cuticle matrix is shielded from premature degradation; however, underlying molecular mechanisms are poorly understood. Previously, we identified the conserved obstructor multigene-family, which encodes chitin-binding proteins. Here we show that Obstructor-A is required for extracellular matrix dynamics in cuticle forming organs. Loss of obstructor-A causes severe defects during cuticle molting, wound protection, tube expansion and larval growth control. We found that Obstructor-A interacts and forms a core complex with the polysaccharide chitin, the cuticle modifier Knickkopf and the chitin deacetylase Serpentine. Knickkopf protects chitin from chitinase-dependent degradation and deacetylase enzymes ensure extracellular matrix maturation. We provide evidence that Obstructor-A is required to control the presence of Knickkopf and Serpentine in the extracellular matrix. We propose a model suggesting that Obstructor-A coordinates the core complex for extracellular matrix protection from premature degradation. This mechanism enables exoskeletal molting, tube expansion, and epithelial integrity. The evolutionary conservation suggests a common role of Obstructor-A and homologs in coordinating extracellular matrix protection in epithelial tissues of chitinous invertebrates.
authors.affiliation: Life & Medical Sciences Institute, LIMES, Laboratory for Molecular Developmental Biology, University of Bonn, Carl-Troll-Strasse 31, 53115 Bonn, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Petkau
authors.forename: Christian
authors.initials: C
authors.lastname: Wingen
authors.forename: Laura C A
authors.initials: LC
authors.lastname: Jussen
authors.forename: Tina
authors.initials: T
authors.lastname: Radtke
authors.forename: Matthias
authors.initials: M
authors.lastname: Behr
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002686:Chitin / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D018978:Molting / Q000502:physiology*; D005810:Multigene Family / Q000502:physiology; D015843:Serpins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; C574473:Obst-A protein, Drosophila; D015843:Serpins; C506753:knk protein, Drosophila; C434683:serpin-2; D002686:Chitin