Laval University Cancer Research Center, CRCHUQ-Hôtel-Dieu de Québec, 9 McMahon, Québec, QC G1R 2J6, Canada.
Curr Biol. 2010 Jan 12;20(1):55-61. doi: 10.1016/j.cub.2009.11.017.
Regulation of epithelial tube size is critical for organ function. However, the mechanisms of tube size control remain poorly understood. In the Drosophila trachea, tube dimensions are regulated by a luminal extracellular matrix (ECM). ECM organization requires apical (luminal) secretion of the protein Vermiform (Verm), which depends on the basolateral septate junction (SJ). Here, we show that apical and basolateral epithelial polarity proteins interact to control tracheal tube size independently of the Verm pathway. Mutations in yurt (yrt) and scribble (scrib), which encode SJ-associated polarity proteins, cause an expansion of tracheal tubes but do not disrupt Verm secretion. Reducing activity of the apical polarity protein Crumbs (Crb) suppresses the length defects in yrt but not scrib mutants, suggesting that Yrt acts by negatively regulating Crb. Conversely, Crb overexpression increases tracheal tube dimensions. Reducing crb dosage also rescues tracheal size defects caused by mutations in coracle (cora), which encodes an SJ-associated polarity protein. In addition, crb mutations suppress cora length defects without restoring Verm secretion. Together, these data indicate that Yrt, Cora, Crb, and Scrib operate independently of the Verm pathway. Our data support a model in which Cora and Yrt act through Crb to regulate epithelial tube size.
上皮管大小的调节对于器官功能至关重要。然而，管大小控制的机制仍知之甚少。在果蝇气管中，管尺寸受腔外基质（ECM）的调节。ECM 的组织需要蛋白质 Vermiform（Verm）的顶端（腔侧）分泌，这依赖于基底外侧的隔膜连接（SJ）。在这里，我们表明，顶端和基底外侧的上皮极性蛋白相互作用，独立于 Verm 途径来控制气管管大小。编码 SJ 相关极性蛋白的 yurt（yrt）和 scribble（scrib）突变导致气管管扩张，但不破坏 Verm 分泌。减少顶端极性蛋白 Crumbs（Crb）的活性抑制 yrt 但不抑制 scrib 突变体的长度缺陷，表明 Yrt 通过负调控 Crb 起作用。相反，Crb 过表达增加气管管尺寸。降低 crb 剂量也可以挽救编码 SJ 相关极性蛋白 coracle（cora）突变引起的气管大小缺陷。此外，crb 突变抑制 cora 长度缺陷而不恢复 Verm 分泌。总之，这些数据表明 Yrt、Cora、Crb 和 Scrib 独立于 Verm 途径发挥作用。我们的数据支持这样一种模型，即 Cora 和 Yrt 通过 Crb 发挥作用来调节上皮管大小。
