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Müller, A. ; Schmidt, D.* ; Xu, C.S.* ; Pang, S.* ; D'Costa, J.V. ; Kretschmar, S.* ; Münster, C. ; Kurth, T.* ; Jug, F.* ; Weigert, M.* ; Hess, H.F.* ; Solimena, M.

3D FIB-SEM reconstruction of microtubule-organelle interaction in whole primary mouse β cells.

J. Cell Biol. 220:e202010039 (2021)

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	Open Access Gold (Paid Option)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Insulin-secretion; Electron-microscopy; Granule Dynamics; High-throughput; In-vivo; Organization; Kinesin; Protein; Visualization; Exocytosis

ISSN (print) / ISBN 0021-9525

e-ISSN 1540-8140

Journal Journal of Cell Biology, The

Quellenangaben Volume: 220, Issue: 2, Article Number: e202010039

Publisher Rockefeller University Press

Publishing Place 950 Third Ave, 2nd Flr, New York, Ny 10022 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Pancreatic Beta Cell Research (IPI)

Grants Howard 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)