Obstructor A Organizes Matrix Assembly at the Apical Cell Surface to Promote Enzymatic Cuticle Maturation in Drosophila
Obstructor A Organizes Matrix Assembly at the Apical Cell Surface to Promote Enzymatic Cuticle Maturation in Drosophila
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DOI：
10.1074/jbc.m114.614933
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发表时间：
2015-04-17
影响因子：
4.8
通讯作者：
Behr, Matthias
中科院分区：
文献类型：
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作者：
Pesch, Yanina-Yasmin;Riedel, Dietmar;Behr, Matthias
顶端细胞外基质（aECM）的组装和成熟对于保护生物体至关重要，但其潜在的分子机制仍然知之甚少。表皮细胞分泌蛋白质和酶，其在顶端细胞表面组装以在发育生长期间和组织损伤时提供上皮完整性和稳定性。我们分析了aECM组装的分子机制，并确定了保守的几丁质结合蛋白Obst-A（Obstructor A）作为一个重要的调节因子。我们表明，在果蝇，Obst-A是需要协调的顶端细胞表面的蛋白质和几丁质基质包装在发展过程中。由表皮细胞分泌，Obst-A蛋白特异性地富集在顶端组装区中，其中基质组分被包装成其高度有序的结构。在obst-A无效突变幼虫中，组装区强烈减少，导致基质支架组织的严重干扰和aECM完整性受损。此外，支持aECM稳定性的酶被错误定位。作为一个生物学后果，角质层结构，完整性和功能在obst-A突变体中受到干扰，最终导致创伤后立即死亡。我们的研究确定了一个新的核心组织中心，组装区，控制aECM组装在顶端细胞表面。我们提出了一种遗传上保守的分子机制，通过这种机制，Obst-A形成了一个基质支架，以协调新沉积的aECM中蛋白质和酶的运输和定位。这种机制对于aECM在生长和重塑上皮组织中作为最外层屏障的成熟和稳定是必不可少的。
Assembly and maturation of the apical extracellular matrix (aECM) is crucial for protecting organisms, but underlying molecular mechanisms remain poorly understood. Epidermal cells secrete proteins and enzymes that assemble at the apical cell surface to provide epithelial integrity and stability during developmental growth and upon tissue damage. We analyzed molecular mechanisms of aECM assembly and identified the conserved chitin-binding protein Obst-A (Obstructor A) as an essential regulator. We show in Drosophila that Obst-A is required to coordinate protein and chitin matrix packaging at the apical cell surface during development. Secreted by epidermal cells, the Obst-A protein is specifically enriched in the apical assembly zone where matrix components are packaged into their highly ordered architecture. In obst-A null mutant larvae, the assembly zone is strongly diminished, resulting in severe disturbance of matrix scaffold organization and impaired aECM integrity. Furthermore, enzymes that support aECM stability are mislocalized. As a biological consequence, cuticle architecture, integrity, and function are disturbed in obst-A mutants, finally resulting in immediate lethality upon wounding. Our studies identify a new core organizing center, the assembly zone that controls aECM assembly at the apical cell surface. We propose a genetically conserved molecular mechanism by which Obst-A forms a matrix scaffold to coordinate trafficking and localization of proteins and enzymes in the newly deposited aECM. This mechanism is essential for maturation and stabilization of the aECM in a growing and remodeling epithelial tissue as an outermost barrier.