Speaker: Kei Sakamoto,
University of Dundee,Scotland UK

Organizer: IRB Barcelona
Host: Dr.Joan Guinovart, IRB Barcelona
Date: Wednesday, 18 January 2012, 13:00 h
Place: Sala Fèlix Serratosa, Parc Cièntific de Barcelona, Spain

Abstract

Glycogen breakdown and synthesis plays a critical role in regulating energy metabolism, glucose homeostasis, and also brain function. Glycogen synthase (GS), a key enzyme in glycogen synthesis, is regulated by the allosteric effector glucose-6-phosphate (G6P) and by covalent control via protein kinases and phosphatases-targeted to glycogen in response to hormones and cellular energy stress. The importance of the allosteric regulation of GS in vivo was unknown, mainly due to the complex interplay between multiple phosphorylation sites and allosteric effectors and also to the lack of a genetic handle on this process. We have solved this previously intractable problem by initially identifying a key amino acid residue required for activation of GS by G6P and then by generating a mouse model in which the normal form of the muscle or liver isoform of GS is replaced by a mutant that cannot bind G6P, but is still capable of being activated normally by dephosphorylation. Using these genetic mouse models, I discuss the importance of allosteric regulation and GS and its impact on cellular glycogen metabolism and glucose homeostasis.