The Na+/K+ ATPase is required for septate junction function and epithelial tube-size control in the Drosophila tracheal system
The Na+/K+ ATPase is required for septate junction function and epithelial tube-size control in the Drosophila tracheal system
复制标题
DOI：
10.1242/dev.00691
复制
发表时间：
2003-10-01
期刊：
影响因子：
4.6
通讯作者：
Beitel, GJ
中科院分区：
文献类型：
--
作者：
Paul, SM;Ternet, M;Beitel, GJ
尽管上皮管的正确结构对于肺、肾和血管系统等器官的功能至关重要，但人们对控制管尺寸的分子机制知之甚少。我们发现 Na+/K+ ATP 酶的 ATPα α 和 nrv2 β 亚基的突变导致果蝇气管的长度增加和直径扩大。 ATPa 和 nrv2 突变还会破坏隔膜连接的稳定形成，这种结构与脊椎动物紧密连接具有一些功能和分子相似性。 Nrv2 β 亚基同种型具有独特的管大小和连接功能，因为 Nrv2（而非其他果蝇 Na+/K+ ATPase P 亚基）可以拯救 nrv2 突变表型。已知隔膜连接基因的突变会导致与 ATPa 和 nrv2 突变相同的气管管尺寸缺陷，表明隔膜连接在上皮管尺寸控制中具有先前未识别的作用。双突变体分析表明，隔膜连接对管大小的控制是由至少两个可辨别的途径介导的，尽管细胞旁扩散屏障功能似乎不参与其中，因为管尺寸控制和扩散屏障功能在遗传上是可分离的。总之，我们的结果表明 Na+/K+ ATP 酶的特定亚型在隔膜连接功能中发挥着至关重要的作用，并且隔膜连接具有调节细胞旁转运和上皮管大小的多种不同功能。
Although the correct architecture of epithelial tubes is crucial for the function of organs such as the lung, kidney and vascular system, little is known about the molecular mechanisms that control tube size. We show that mutations in the ATPalpha alpha and nrv2 beta subunits of the Na+/K+ ATPase cause Drosophila tracheal tubes to have increased lengths and expanded diameters. ATPa and nrv2 mutations also disrupt stable formation of septate junctions, structures with some functional and molecular similarities to vertebrate tight junctions. The Nrv2 beta subunit isoforms have unique tube size and junctional functions because Nrv2, but not other Drosophila Na+/K+ ATPase P subunits, can rescue nrv2 mutant phenotypes. Mutations in known septate junctions genes cause the same tracheal tube-size defects as ATPa and nrv2 mutations, indicating that septate junctions have a previously unidentified role in epithelial tube-size control. Double mutant analyses suggest that tube-size control by septate junctions is mediated by at least two discernable pathways, although the paracellular diffusion barrier function does not appear to involved because tube-size control and diffusion barrier function are genetically separable. Together, our results demonstrate that specific isoforms of the Na+/K+ ATPase play a crucial role in septate junction function and that septate junctions have multiple distinct functions that regulate paracellular transport and epithelial tube size.