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Visualizing subcellular rearrangements in intact ß cells using soft x-ray tomography.
White, Kate L; Singla, Jitin; Loconte, Valentina; Chen, Jian-Hua; Ekman, Axel; Sun, Liping; Zhang, Xianjun; Francis, John Paul; Li, Angdi; Lin, Wen; Tseng, Kaylee; McDermott, Gerry; Alber, Frank; Sali, Andrej; Larabell, Carolyn; Stevens, Raymond C.
Affiliation
  • 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.
  • Singla J; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Loconte V; Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Chen JH; Institute for Quantitative and Computational Biosciences, Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ekman A; iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  • Sun L; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Zhang X; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Francis JP; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Li A; iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  • Lin W; Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Tseng K; Department of Computer Science, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • McDermott G; iHuman Institute, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  • Alber F; Department of Chemistry, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Sali A; Department of Biological Sciences, Bridge Institute, USC Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, CA 90089, USA.
  • Larabell C; Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • Stevens RC; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Sci Adv ; 6(50)2020 12.
Article in En | MEDLINE | ID: mdl-33298443
ABSTRACT
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 ß 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.

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Sci Adv Year: 2020 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Sci Adv Year: 2020 Document type: Article