Institute of Genetics, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Elife. 2020 Dec 30;9:e61866. doi: 10.7554/eLife.61866.
Loss of ESCRT function in imaginal discs is known to cause neoplastic overgrowth fueled by mis-regulation of signaling pathways. Its impact on junctional integrity, however, remains obscure. To dissect the events leading to neoplasia, we used transmission electron microscopy (TEM) on wing imaginal discs temporally depleted of the ESCRT-III core component Shrub. We find a specific requirement for Shrub in maintaining septate junction (SJ) integrity by transporting the claudin Megatrachea (Mega) to the SJ. In absence of Shrub function, Mega is lost from the SJ and becomes trapped on endosomes coated with the endosomal retrieval machinery retromer. We show that ESCRT function is required for apical localization and mobility of retromer positive carrier vesicles, which mediate the biosynthetic delivery of Mega to the SJ. Accordingly, loss of retromer function impairs the anterograde transport of several SJ core components, revealing a novel physiological role for this ancient endosomal agent.
已知胚胎盘内 ESCRT 功能的丧失会导致信号通路失调引起的肿瘤过度生长。然而，其对连接完整性的影响尚不清楚。为了剖析导致肿瘤发生的事件，我们使用透射电子显微镜 (TEM) 对暂时耗尽 ESCRT-III 核心成分 Shrub 的翅膀胚胎盘进行了研究。我们发现，Shrub 通过将 Claudin Megatrachea (Mega) 运输到 SJ 中，特异性地维持了隔膜连接 (SJ) 的完整性。在没有 Shrub 功能的情况下，Mega 会从 SJ 中丢失，并被困在内体上，这些内体被内体回收机制 retromer 覆盖。我们表明 ESCRT 功能对于 retromer 阳性载体囊泡的顶端定位和迁移是必需的，这些载体囊泡介导了 Mega 到 SJ 的生物合成递呈。因此，retromer 功能的丧失会损害几个 SJ 核心成分的顺行运输，这揭示了这个古老的内体因子的新的生理作用。
