Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis.

Clara Prats; Joan A Cadefau; Roser Cussó; Klaus Qvortrup; Jakob N Nielsen; Jørgen Wojtaszewski; D Grahame Hardie; Greg Stewart; Bo F Hansen; Thorkil Ploug

doi:10.1074/jbc.M502713200

Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis.

Clara Prats, Joan A Cadefau, Roser Cussó, Klaus Qvortrup, Jakob N Nielsen, Jørgen Wojtaszewski, D Grahame Hardie, Greg Stewart, Bo F Hansen, Thorkil Ploug

53 Citations (Scopus)

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.

Original language	English
Journal	Journal of Biological Chemistry
Volume	280
Issue number	24
Pages (from-to)	23165-72
Number of pages	7
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.M502713200
Publication status	Published - 2005

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10.1074/jbc.M502713200

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@article{96eaee30abfc11ddb5e9000ea68e967b,

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.",

author = "Clara Prats and Cadefau, {Joan A} and Roser Cuss{\'o} and Klaus Qvortrup and Nielsen, {Jakob N} and J{\o}rgen Wojtaszewski and Hardie, {D Grahame} and Greg Stewart and Hansen, {Bo F} and Thorkil Ploug",

note = "Keywords: Actins; Adenosine Monophosphate; Allosteric Site; Amino Acid Sequence; Animals; Centrifugation; Cytoplasm; Cytoskeleton; Female; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Image Processing, Computer-Assisted; Immunohistochemistry; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Molecular Sequence Data; Muscle, Skeletal; Muscles; Peptides; Phosphorylation; Protein Conformation; Protein Structure, Tertiary; Protein Transport; Rabbits; Sarcoplasmic Reticulum; Subcellular Fractions; Tibia; Time Factors",

year = "2005",

doi = "10.1074/jbc.M502713200",

language = "English",

volume = "280",

pages = "23165--72",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

number = "24",

}

TY - JOUR

T1 - Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis.

AU - Prats, Clara

AU - Cadefau, Joan A

AU - Cussó, Roser

AU - Qvortrup, Klaus

AU - Nielsen, Jakob N

AU - Wojtaszewski, Jørgen

AU - Hardie, D Grahame

AU - Stewart, Greg

AU - Hansen, Bo F

AU - Ploug, Thorkil

N1 - Keywords: Actins; Adenosine Monophosphate; Allosteric Site; Amino Acid Sequence; Animals; Centrifugation; Cytoplasm; Cytoskeleton; Female; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Image Processing, Computer-Assisted; Immunohistochemistry; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Molecular Sequence Data; Muscle, Skeletal; Muscles; Peptides; Phosphorylation; Protein Conformation; Protein Structure, Tertiary; Protein Transport; Rabbits; Sarcoplasmic Reticulum; Subcellular Fractions; Tibia; Time Factors

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M502713200

DO - 10.1074/jbc.M502713200

M3 - Journal article

C2 - 15840572

SN - 0021-9258

VL - 280

SP - 23165

EP - 23172

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 24

ER -

Phosphorylation-dependent translocation of glycogen synthase to a novel structure during glycogen resynthesis.

Abstract

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