A NEW LEVEL OF REGULATION IN GLUCONEOGENESIS: METABOLIC STATE MODULATES THE INTRACELLULAR LOCALIZATION OF ALDOLASE B AND ITS INTERACTION WITH LIVER FRUCTOSE-1,6-BISPHOSPHATASE Droppelmann

We observed that glucose, insulin, glucagon and adrenaline differentially modulate the intracellular distribution of aldolase-B and FBPase-1. Interestingly, the in vitro protein-protein interaction analysis between aldolase-B and FBPase-1 showed a specific and regulatable interaction between them, whereas aldolase-A (muscle isozyme) and FBPase-1 showed no interaction. The affinity of the aldolase-B and FBPase-1 complex was modulated by intermediate metabolites, but only in the presence of K. We observed a decreased association constant in the presence of AMP, fructose-2,6-bisphosphate, fructose-6-phosphate and inhibitory concentrations of fructose-1,6-bisphosphate. Conversely, the association constant of the complex increased in the presence of dihydroxyacetone phosphate and non-inhibitory concentrations of fructose-1,6-bisphosphate. Notably, in vivo FRET studies confirmed the interaction between aldolase-B and FBPase-1. Also, the co-expression of aldolase-B and FBPase-1 in cultured cells suggested that FBPase-1 guides the cellular localization of aldolaseB.