Glucose as a Protein-Condensing Cellular Solute

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.