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Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo
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Glucose as a Protein-Condensing Cellular Solute.

Naotaka Noda1,2, Yejin Jung1,2, Genyir Ado1,2

  • 1Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.

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|February 21, 2022
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Glucose unexpectedly causes protein aggregation, a phenomenon termed "glucosing-out." This study found that glucose induces precipitation in cellular proteins like calmodulin, impacting cellular processes and homeostasis.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Proteomics

Background:

  • Chemical library screening revealed an unexpected
  • glucosing-out
  • effect where glucose induced compound aggregation.
  • This observation prompted an investigation into glucose's effect on proteins.

Purpose of the Study:

  • To investigate the protein-condensing effect of glucose.
  • To identify cellular proteins that undergo glucose-dependent precipitation.
  • To explore the functional implications of glucose-induced protein phase separation.

Main Methods:

  • Proteomic analysis was employed to identify proteins affected by glucose.
  • The precipitation of specific proteins, including calmodulin, was analyzed under varying glucose concentrations.
  • Cellular assays were performed to assess the functional impact of glucose-dependent calmodulin condensates on glycogenolysis.

Main Results:

  • Three cellular proteins, including calmodulin, rho guanine nucleotide exchange factor 40, and polyubiquitin-C, exhibited glucose-dependent precipitation.
  • Calmodulin formed distinct glucose-dependent condensates.
  • These calmodulin condensates were found to regulate glycogenolysis in hepatic cells.

Conclusions:

  • Glucose is a significant, previously unrecognized driver of protein phase separation.
  • Glucose-induced protein condensation can influence critical cellular processes like glycogenolysis.
  • These findings suggest a novel mechanism impacting cellular homeostasis through glucose-protein interactions.