Luschnig Stefan, Bätz Tilmann, Armbruster Kristina, Krasnow Mark A
Bayreuther Zentrum für Molekulare Biowissenschaften, Department of Genetics, University of Bayreuth, D-95440 Bayreuth, Germany.
Curr Biol. 2006 Jan 24;16(2):186-94. doi: 10.1016/j.cub.2005.11.072.
Many organs contain epithelial tubes that transport gases or liquids . Proper tube size and shape is crucial for organ function, but the mechanisms controlling tube diameter and length are poorly understood. Recent studies of tracheal (respiratory) tube morphogenesis in Drosophila show that chitin synthesis genes produce an expanding chitin cylinder in the apical (luminal) extracellular matrix (ECM) that coordinates the dilation of the surrounding epithelium . Here, we describe two genes involved in chitin modification, serpentine (serp) and vermiform (verm), mutations in which cause excessively long and tortuous tracheal tubes. The genes encode similar proteins with an LDL-receptor ligand binding motif and chitin binding and deacetylation domains. Both proteins are expressed and secreted during tube expansion and localize throughout the lumen in a chitin-dependent manner. Unlike previously characterized chitin pathway genes, serp and verm are not required for chitin synthesis or secretion but rather for its normal fibrillar structure. The mutations also affect structural properties of another chitinous matrix, epidermal cuticle. Our work demonstrates that chitin and the matrix proteins Serp and Verm limit tube elongation, and it suggests that tube length is controlled independently of diameter by modulating physical properties of the chitin ECM, presumably by N-deacetylation of chitin and conversion to chitosan.
许多器官都含有用于运输气体或液体的上皮管。合适的管径和形状对器官功能至关重要，但控制管径和长度的机制却鲜为人知。最近对果蝇气管（呼吸）管形态发生的研究表明，几丁质合成基因在顶端（管腔）细胞外基质（ECM）中产生一个不断扩大的几丁质圆柱体，该圆柱体协调周围上皮细胞的扩张。在此，我们描述了两个参与几丁质修饰的基因，蜿蜒（serp）和蠕虫状（verm），其突变会导致气管管过长且扭曲。这两个基因编码的蛋白质相似，具有低密度脂蛋白受体配体结合基序以及几丁质结合和脱乙酰化结构域。两种蛋白质在管扩张过程中表达并分泌，并以几丁质依赖的方式定位于整个管腔。与先前表征的几丁质途径基因不同，serp和verm并非几丁质合成或分泌所必需，而是其正常纤维状结构所必需。这些突变还影响另一种几丁质基质——表皮角质层的结构特性。我们的研究表明，几丁质以及基质蛋白Serp和Verm限制了管的伸长，并且表明管的长度是通过调节几丁质ECM的物理特性独立于直径进行控制的，推测是通过几丁质的N - 脱乙酰化并转化为壳聚糖来实现的。
