Hematology and Oncology, University Medical Center Goettingen, 37075 Goettingen, Germany.
Developmental Biochemistry, University Medical Center Goettingen, 37077 Goettingen, Germany.
Development. 2020 Aug 14;147(15):dev186833. doi: 10.1242/dev.186833.
Development and tissue homeostasis rely on the tight regulation of morphogen secretion. In the wing imaginal disc epithelium, Wg secretion for long-range signal transduction occurs after apical Wg entry into the endosomal system, followed by secretory endosomal transport. Although Wg release appears to occur from the apical and basal cell sides, its exact post-endocytic fate and the functional relevance of polarized endosomal Wg trafficking are poorly understood. Here, we identify the kinesin-3 family member Klp98A as the master regulator of intracellular Wg transport after apical endocytosis. In the absence of Klp98A, functional mature endosomes accumulate in the apical cytosol, and endosome transport to the basal cytosol is perturbed. Despite the resulting Wg mislocalization, Wg signal transduction occurs normally. We conclude that transcytosis-independent routes for Wg trafficking exist and demonstrate that Wg can be recycled apically via Rab4-recycling endosomes in the absence of Klp98A.
发育和组织稳态依赖于形态发生素分泌的紧密调节。在 翅 imaginal 盘上皮细胞中，Wg 的长距离信号转导发生在 Wg 进入内体系统的顶端之后，随后是分泌内体运输。尽管 Wg 的释放似乎发生在顶端和基底细胞侧，但内体后 Wg 的确切命运及其极化内体 Wg 运输的功能相关性尚不清楚。在这里，我们确定了驱动蛋白-3 家族成员 Klp98A 是顶端内吞作用后细胞内 Wg 运输的主要调节因子。在 Klp98A 缺失的情况下，功能性成熟的内体在顶端细胞质中积累，并且内体向基底细胞质的运输受到干扰。尽管导致 Wg 定位错误，但 Wg 信号转导仍正常发生。我们得出结论，存在与胞吐作用无关的 Wg 运输途径，并证明在 Klp98A 缺失的情况下，Wg 可以通过 Rab4 再循环内体从顶端重新循环。
