Visualizing subcellular rearrangements in intact β cells using soft x-ray tomography
Author(s) -
Kate L. White,
Jitin Singla,
Valentina Loconte,
Jian-Hua Chen,
Axel Ekman,
Liping Sun,
Xianjun Zhang,
John Paul Francis,
Angdi Li,
Wen Lin,
Kaylee Tseng,
Gerry McDermott,
Frank Alber,
Andrej Šali,
Carolyn A. Larabell,
Raymond C. Stevens
Publication year - 2020
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abc8262
Subject(s) - organelle , vesicle , stimulation , secretory vesicle , microbiology and biotechnology , insulin , secretion , mitochondrion , biophysics , biology , cell , chemistry , exocytosis , biochemistry , endocrinology , membrane
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.
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