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Determinants of the nucleocytoplasmic shuttling of muscle glycogen synthase
Author(s) -
Cid Emili,
Cifuentes Daniel,
Baqué Susanna,
Ferrer Juan C.,
Guinovart Joan J.
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04738.x
Subject(s) - nuclear export signal , nuclear transport , nuclear localization sequence , biology , glycogen synthase , glycogen , phosphorylation , cytoplasm , allosteric regulation , cajal body , cell nucleus , nuclear protein , microbiology and biotechnology , biochemistry , glycogen debranching enzyme , enzyme , transcription factor , gene , rna , rna splicing
Muscle glycogen synthase (MGS) presents a nuclear speckled pattern in primary cultured human muscle and in 3T3‐L1 cells deprived of glucose and with depleted glycogen reserves. Nuclear accumulation of the enzyme correlates inversely with cellular glycogen content. Although the glucose‐induced export of MGS from the nucleus to the cytoplasm is blocked by leptomycin B, and therefore mediated by CRM1, no nuclear export signal was identified in the sequence of the protein. Deletion analysis shows that the region comprising amino acids 555–633 of human MGS, which encompasses an Arg‐rich cluster involved in the allosteric activation of the enzyme by Glc6 P , is crucial for its nuclear concentration and aggregation. Mutation of these Arg residues, which desensitizes the enzyme towards Glc6 P , interferes with its nuclear accumulation. In contrast, the known phosphorylation sites of MGS that regulate its activity are not involved in the control of its subcellular distribution. Nuclear human MGS colocalizes with the promyelocytic leukaemia oncoprotein and p80‐coilin, a marker of Cajal bodies. The subnuclear distribution of MGS is altered by incubation with transcription inhibitors. These observations suggest that, in addition to its metabolic function, MGS may participate in nuclear processes.