Glucose as a Protein-Condensing Cellular Solute

ACS Chem Biol. 2022 Mar 18;17(3):567-575. doi: 10.1021/acschembio.1c00849. Epub 2022 Feb 21.

Abstract

The present study reports a surprising protein-condensing effect of glucose, prompted by our accidental observation during chemical library screening under a high-glucose condition. We noticed "glucosing-out" of certain compounds, in which physiological concentrations of glucose induced compound aggregation. Adapting the "glucosing-out" concept to proteins, our proteomic analysis identified three cellular proteins (calmodulin, rho guanine nucleotide exchange factor 40, and polyubiquitin-C) that displayed robust glucose-dependent precipitation. One of these proteins, calmodulin, formed glucose-dependent condensates that control cellular glycogenolysis in hepatic cells. Our findings suggest that glucose is a heretofore underappreciated driver of protein phase separation that may have profound effects on cellular homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calmodulin / metabolism
  • Glucose* / metabolism
  • Glycogenolysis*
  • Homeostasis
  • Proteomics

Substances

  • Calmodulin
  • Glucose