Molecular Diabetology, University Hospital and Faculty of Medicine, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Paul Langerhans Institute Dresden of the Helmholtz Center Munich at the University Hospital and Faculty of Medicine, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
J Cell Biol. 2021 Feb 1;220(2). doi: 10.1083/jcb.202010039.
Microtubules play a major role in intracellular trafficking of vesicles in endocrine cells. Detailed knowledge of microtubule organization and their relation to other cell constituents is crucial for understanding cell function. However, their role in insulin transport and secretion is under debate. Here, we use FIB-SEM to image islet β cells in their entirety with unprecedented resolution. We reconstruct mitochondria, Golgi apparati, centrioles, insulin secretory granules, and microtubules of seven β cells, and generate a comprehensive spatial map of microtubule-organelle interactions. We find that microtubules form nonradial networks that are predominantly not connected to either centrioles or endomembranes. Microtubule number and length, but not microtubule polymer density, vary with glucose stimulation. Furthermore, insulin secretory granules are enriched near the plasma membrane, where they associate with microtubules. In summary, we provide the first 3D reconstructions of complete microtubule networks in primary mammalian cells together with evidence regarding their importance for insulin secretory granule positioning and thus their supportive role in insulin secretion.
微管在内分泌细胞的囊泡细胞内运输中起着重要作用。详细了解微管的组织及其与其他细胞成分的关系对于理解细胞功能至关重要。然而，它们在胰岛素运输和分泌中的作用仍存在争议。在这里，我们使用 FIB-SEM 以前所未有的分辨率对完整的胰岛β细胞进行成像。我们重建了七个β细胞中的线粒体、高尔基体装置、中心粒、胰岛素分泌颗粒和微管，并生成了微管-细胞器相互作用的综合空间图谱。我们发现微管形成非径向网络，主要与中心粒或内膜系统没有连接。微管的数量和长度会随着葡萄糖的刺激而变化，但微管聚合物的密度不会变化。此外，胰岛素分泌颗粒在靠近质膜的地方富集，在那里它们与微管结合。总之，我们提供了第一个完整的哺乳动物细胞微管网络的 3D 重建，并提供了有关其对胰岛素分泌颗粒定位重要性的证据，从而支持其在胰岛素分泌中的作用。
