Obstructor-A Is Required for Epithelial Extracellular Matrix Dynamics, Exoskeleton Function, and Tubulogenesis
Obstructor-A Is Required for Epithelial Extracellular Matrix Dynamics, Exoskeleton Function, and Tubulogenesis
复制标题
DOI：
10.1074/jbc.m112.359984
复制
发表时间：
2012-06-15
影响因子：
4.8
通讯作者：
Behr, Matthias
中科院分区：
文献类型：
--
作者：
Petkau, Georg;Wingen, Christian;Behr, Matthias
表皮和内部管状器官，如肠和肺，暴露在恶劣的环境中。它们形成细胞外基质以提供上皮完整性并防止与病原体和毒素接触。在节肢动物中，角质层保护，形状，并使器官的功能。在发育过程中，角质层基质不会过早降解;然而，对潜在的分子机制知之甚少。在此之前，我们发现了一个保守的多基因家族，它编码几丁质结合蛋白。在这里，我们表明，障碍物-A是所需的角质层形成器官的细胞外基质动力学。障碍物-A的损失在角质层蜕皮、伤口保护、管扩张和幼虫生长控制期间引起严重缺陷。我们发现，障碍物-A相互作用，并形成一个核心复合物的多糖甲壳素，角质层改性剂Knickkopf和甲壳素脱乙酰酶丝氨酸。Knickkopf保护几丁质免于几丁质酶依赖性降解，脱乙酰酶确保细胞外基质成熟。我们提供的证据表明，障碍物-A是需要控制的细胞外基质中的尼克科夫和丝氨酸蛋白酶的存在。我们提出了一个模型，表明障碍-A协调核心复合物的细胞外基质保护过早降解。这种机制使外骨骼蜕皮，管扩张，和上皮完整性。进化的保守性表明，在协调几丁质无脊椎动物上皮组织的细胞外基质保护的障碍A和同系物的共同作用。
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.