title: Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis.
abstract: Glycogen metabolism has been the subject of extensive research, but the mechanisms by which it is regulated are still not fully understood. It is well accepted that the rate-limiting enzymes in glycogenesis and glycogenolysis are glycogen synthase (GS) and glycogen phosphorylase (GPh), respectively. Both enzymes are regulated by reversible phosphorylation and by allosteric effectors. However, evidence in the literature indicates that changes in muscle GS and GPh intracellular distribution may constitute a new regulatory mechanism of glycogen metabolism. Already in the 1960s, it was proposed that glycogen was present in dynamic cellular organelles that were termed glycosomas but no such cellular entities have ever been demonstrated. The aim of this study was to characterize muscle GS and GPh intracellular distribution and to identify possible translocation processes of both enzymes. Using in situ stimulation of rabbit tibialis anterior muscle, we show GS and GPh intracellular redistribution at the beginning of glycogen resynthesis after contraction-induced glycogen depletion. We identify a new "player," a new intracellular compartment involved in skeletal muscle glycogen metabolism. They are spherical structures that were not present in basal muscle, and we present evidence that indicate that they are products of actin cytoskeleton remodeling. Furthermore, for the first time, we show a phosphorylation-dependent intracellular distribution of GS. Here, we present evidence of a new regulatory mechanism of skeletal muscle glycogen metabolism based on glycogen enzyme intracellular compartmentalization.
authors.affiliation: Copenhagen Muscle Research Centre, University of Copenhagen, Denmark. cprats@mfi.ku.dk
authors.forename: Clara
authors.initials: C
authors.lastname: Prats
authors.forename: Joan A
authors.initials: JA
authors.lastname: Cadefau
authors.forename: Roser
authors.initials: R
authors.lastname: Cussó
authors.forename: Klaus
authors.initials: K
authors.lastname: Qvortrup
authors.forename: Jakob N
authors.initials: JN
authors.lastname: Nielsen
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewki
authors.forename: D Grahame
authors.initials: DG
authors.lastname: Hardie
authors.forename: Greg
authors.initials: G
authors.lastname: Stewart
authors.forename: Bo F
authors.initials: BF
authors.lastname: Hansen
authors.forename: Thorkil
authors.initials: T
authors.lastname: Ploug
mesh_terms: D000199:Actins / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000737:chemistry; D000495:Allosteric Site; D000595:Amino Acid Sequence; D000818:Animals; D002498:Centrifugation; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D006003:Glycogen / Q000737:chemistry* / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000737:chemistry* / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D009132:Muscles / Q000201:enzymology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000378:metabolism; D013977:Tibia / Q000378:metabolism; D013997:Time Factors
chemical_list: D000199:Actins; D010455:Peptides; D000249:Adenosine Monophosphate; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase