Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
12 2020
Historique:
received: 15 05 2020
accepted: 21 10 2020
entrez: 10 12 2020
pubmed: 11 12 2020
medline: 11 12 2020
Statut: epublish

Résumé

Characterizing relationships between cell structures and functions requires mesoscale mapping of intact cells showing subcellular rearrangements following stimulation; however, current approaches are limited in this regard. Here, we report a unique application of soft x-ray tomography to generate three-dimensional reconstructions of whole pancreatic β cells at different time points following glucose-stimulated insulin secretion. Reconstructions following stimulation showed distinct insulin vesicle distribution patterns reflective of altered vesicle pool sizes as they travel through the secretory pathway. Our results show that glucose stimulation caused rapid changes in biochemical composition and/or density of insulin packing, increased mitochondrial volume, and closer proximity of insulin vesicles to mitochondria. Costimulation with exendin-4 (a glucagon-like peptide-1 receptor agonist) prolonged these effects and increased insulin packaging efficiency and vesicle maturation. This study provides unique perspectives on the coordinated structural reorganization and interactions of organelles that dictate cell responses.

Identifiants

pubmed: 33298443
pii: 6/50/eabc8262
doi: 10.1126/sciadv.abc8262
pmc: PMC7725475
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIGMS NIH HHS
ID : P30 GM138441
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103445
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM109824
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM083960
Pays : United States

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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Auteurs

Kate L White (KL)

Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. stevens@usc.edu calarabell@lbl.gov sali@salilab.org katewhit@usc.edu.
Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.

Jitin Singla (J)

Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Valentina Loconte (V)

iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Jian-Hua Chen (JH)

Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.

Axel Ekman (A)

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.

Liping Sun (L)

iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Xianjun Zhang (X)

Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.

John Paul Francis (JP)

Department of Computer Science, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.

Angdi Li (A)

iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Wen Lin (W)

Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.

Kaylee Tseng (K)

Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.

Gerry McDermott (G)

Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.

Frank Alber (F)

Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Andrej Sali (A)

California Institute for Quantitative Biosciences, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA. stevens@usc.edu calarabell@lbl.gov sali@salilab.org katewhit@usc.edu.

Carolyn Larabell (C)

Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. stevens@usc.edu calarabell@lbl.gov sali@salilab.org katewhit@usc.edu.
Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.

Raymond C Stevens (RC)

Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA. stevens@usc.edu calarabell@lbl.gov sali@salilab.org katewhit@usc.edu.
iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.

Classifications MeSH