title: Localization and regulation of the N terminal splice variant of PGC-1α in adult skeletal muscle fibers.
abstract: The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) regulates expression of genes for metabolism and muscle fiber type. Recently, a novel splice variant of PGC-1α (NT-PGC-1α, amino acids 1-270) was cloned and found to be expressed in muscle. Here we use Flag-tagged NT-PGC-1α to examine the subcellular localization and regulation of NT-PGC-1α in skeletal muscle fibers. Flag-NT-PGC-1α is located predominantly in the myoplasm. Nuclear NT-PGC-1α can be increased by activation of protein kinase A. Activation of p38 MAPK by muscle activity or of AMPK had no effect on the subcellular distribution of NT-PGC-1α. Inhibition of CRM1-mediated export only caused relatively slow nuclear accumulation of NT-PGC-1α, indicating that nuclear export of NT-PGC-1α may be mediated by both CRM1-dependent and -independent pathways. Together these results suggest that the regulation of NT-PGC-1α in muscle fibers may be very different from that of the full-length PGC-1α, which is exclusively nuclear.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201-1503, USA.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Shen
authors.forename: Yewei
authors.initials: Y
authors.lastname: Liu
authors.forename: Martin F
authors.initials: MF
authors.lastname: Schneider
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D028884:Karyopherins / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000097606:Exportin 1 Protein
chemical_list: D055372:AMP-Activated Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D028884:Karyopherins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C485290:Ppargc1a protein, mouse