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.
Institut(e)Institute for Pancreatic Beta Cell Research (IPI)
FörderungenHoward Hughes Medical Institute GermanIsraeli Foundation for Scientific Research and Development (GIF) German Research Foundation (DFG) Agence Nationale de la Recherche Innovative Medicines Initiative 2 Joint Undertaking European Union's Framework Program Horizon 2020 EFPIA Swiss State Secretariat for Education, Research and Innovation JDRF International Leona M. and Harry B. Helmsley Charitable Trust MeDDrive grant from the Carl Gustav Carus Faculty of Medicine at TU Dresden European Fund for Regional Development German Center for Diabetes Research (DZD e.V.) by the German Ministry for Education and Research (BMBF)