Obstructor-A Is Required for Epithelial Extracellular Matrix Dynamics, Exoskeleton Function, and Tubulogenesis

• Published in: The Journal of biological chemistry 2012-06, Vol.287 (25), p.21396-21405
• Main Authors: Petkau, Georg, Wingen, Christian, Jussen, Laura C.A., Radtke, Tina, Behr, Matthias
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - genetics; Carrier Proteins - metabolism; Chitin; Chitin - genetics; Chitin - metabolism; Chitinase; Developmental Biology; Drosophila; Drosophila melanogaster; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Epidermis; Epithelial Cell; Epithelium - metabolism; Exoskeleton; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Extracellular Matrix Proteins; Molting - physiology; Multigene Family - physiology; Serpins - genetics; Serpins - metabolism; Tubulogenesis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.359984

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. The extracellular matrix (ECM) is essential for protection and development of epithelial tissues. Obstructor-A (Obst-A) organizes a core complex with chitin modifiers and enzymes to protect ECM from premature degradation. Obst-A is required for growth control, tubulogenesis, wound healing, and epithelial integrity. This novel mechanism is crucial for understanding ECM dynamics of epithelial tissues.