Kinesin-directed secretion of basement membrane proteins to a subdomain of the basolateral surface in Drosophila epithelial cells.
Kinesin-directed secretion of basement membrane proteins to a subdomain of the basolateral surface in Drosophila epithelial cells.
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DOI：
10.1016/j.cub.2021.12.025
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发表时间：
2022-02-28
期刊：
影响因子：
--
通讯作者：
Horne-Badovinac S
中科院分区：
文献类型：
--
作者：
Zajac AL;Horne-Badovinac S
上皮组织在其基底表面衬有片状基底膜（BM）细胞外基质，其在粘附和信号传导中起重要作用。BM还提供机械支持以引导形态发生。尽管它们很重要，但我们对上皮细胞在发育过程中如何分泌和组装BM知之甚少。BM蛋白被分选到与其他基底外侧蛋白不同的基底外侧分泌途径中。由于BM蛋白自组装成网络和BM线只有基底外侧域的一小部分，我们假设，BM蛋白分泌的网站可能受到严格控制。使用果蝇滤泡上皮，我们表明，驱动蛋白-3和驱动蛋白-1电机一起工作，以确定这个分泌网站。与所有上皮细胞一样，滤泡细胞沿其顶基轴沿着有极化微管（MT）。这些细胞集体迁移，并且它们在其基底表面也具有沿迁移轴沿着极化的MT。我们发现滤泡细胞MT形成一个相互连接的网络，这使得驱动蛋白可以将Rab 10 + BM分泌囊泡从基底部运输到每个细胞的后缘。这将它们定位在基底表面附近和侧域的最基底区域用于胞吐。当驱动蛋白转运被破坏时，BM蛋白分泌的位点扩大，并且在细胞之间形成异位BM网络，其阻碍迁移并破坏组织结构。这些结果显示了上皮细胞如何通过基于MT的转运在其基底外侧表面上定义一个子域，并突出了控制网络形成蛋白的胞吐位点的重要性。
Epithelial tissues are lined with a sheet-like basement membrane (BM) extracellular matrix at their basal surfaces that plays essential roles in adhesion and signaling. BMs also provide mechanical support to guide morphogenesis. Despite their importance, we know little about how epithelial cells secrete and assemble BMs during development. BM proteins are sorted into a basolateral secretory pathway distinct from other basolateral proteins. Because BM proteins self-assemble into networks and the BM lines only a small portion of the basolateral domain, we hypothesized that the site of BM protein secretion might be tightly controlled. Using the Drosophila follicular epithelium, we show that kinesin-3 and kinesin-1 motors work together to define this secretion site. Like all epithelia, the follicle cells have polarized microtubules (MT) along their apical-basal axes. These cells collectively migrate, and they also have polarized MTs along the migratory axis at their basal surfaces. We find follicle cell MTs form one interconnected network, which allows kinesins to transport Rab10+ BM secretory vesicles both basally and to the trailing edge of each cell. This positions them near the basal surface and the basal-most region of the lateral domain for exocytosis. When kinesin transport is disrupted, the site of BM protein secretion is expanded, and ectopic BM networks form between cells that impede migration and disrupt tissue architecture. These results show how epithelial cells can define a subdomain on their basolateral surface through MT-based transport and highlight the importance of controlling the exocytic site of network-forming proteins.
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发表时间：
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期刊：
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