Université Clermont Auvergne, Institute of Genetics, Reproduction and Development (iGReD), UMR CNRS 6293-INSERM U1103, Faculté de Médecine, Clermont-Ferrand, France.
PLoS Genet. 2024 Mar 4;20(3):e1011169. doi: 10.1371/journal.pgen.1011169. eCollection 2024 Mar.
The basement membrane (BM) is an essential structural element of tissues, and its diversification participates in organ morphogenesis. However, the traffic routes associated with BM formation and the mechanistic modulations explaining its diversification are still poorly understood. Drosophila melanogaster follicular epithelium relies on a BM composed of oriented BM fibrils and a more homogenous matrix. Here, we determined the specific molecular identity and cell exit sites of BM protein secretory routes. First, we found that Rab10 and Rab8 define two parallel routes for BM protein secretion. When both routes were abolished, BM production was fully blocked; however, genetic interactions revealed that these two routes competed. Rab10 promoted lateral and planar-polarized secretion, whereas Rab8 promoted basal secretion, leading to the formation of BM fibrils and homogenous BM, respectively. We also found that the dystrophin-associated protein complex (DAPC) and Rab10 were both present in a planar-polarized tubular compartment containing BM proteins. DAPC was essential for fibril formation and sufficient to reorient secretion towards the Rab10 route. Moreover, we identified a dual function for the exocyst complex in this context. First, the Exo70 subunit directly interacted with dystrophin to limit its planar polarization. Second, the exocyst complex was also required for the Rab8 route. Altogether, these results highlight important mechanistic aspects of BM protein secretion and illustrate how BM diversity can emerge from the spatial control of distinct traffic routes.
基底膜(BM)是组织的重要结构元素,其多样化参与器官形态发生。然而,与 BM 形成相关的运输途径以及解释其多样化的机械调节仍然知之甚少。果蝇滤泡上皮依赖于由定向 BM 纤维和更均匀的基质组成的 BM。在这里,我们确定了 BM 蛋白分泌途径的特定分子身份和细胞出口点。首先,我们发现 Rab10 和 Rab8 定义了 BM 蛋白分泌的两条平行途径。当这两种途径都被阻断时,BM 的产生完全被阻断;然而,遗传相互作用表明这两种途径是竞争的。Rab10 促进侧向和平面极化分泌,而 Rab8 促进基底分泌,分别导致 BM 纤维和均匀 BM 的形成。我们还发现,肌营养不良相关蛋白复合物(DAPC)和 Rab10 都存在于包含 BM 蛋白的平面极化管状隔室中。DAPC 对于纤维形成是必不可少的,足以将分泌重新定向到 Rab10 途径。此外,我们在这种情况下确定了外核蛋白复合物的双重功能。首先,Exo70 亚基与肌营养不良蛋白直接相互作用,限制其平面极化。其次,外核蛋白复合物对于 Rab8 途径也是必需的。总而言之,这些结果突出了 BM 蛋白分泌的重要机制方面,并说明了如何从不同交通途径的空间控制中出现 BM 多样性。