title: A karyopherin alpha2 nuclear transport pathway is regulated by glucose in hepatic and pancreatic cells.
abstract: We studied the role of the karyopherin alpha2 nuclear import carrier (also known as importin alpha2) in glucose signaling. In mhAT3F hepatoma cells, GFP-karyopherin alpha2 accumulated massively in the cytoplasm within minutes of glucose extracellular addition and returned to the nucleus after glucose removal. In contrast, GFP-karyopherin alpha1 distribution was unaffected regardless of glucose concentration. Glucose increased GFP-karyopherin alpha2 nuclear efflux by a factor 80 and its shuttling by a factor 4. These glucose-induced movements were not due to glycolytic ATP production. The mechanism involved was leptomycin B-insensitive, but phosphatase- and energy-dependent. HepG2 and COS-7 cells displayed no glucose-induced GFP-karyopherin alpha2 movements. In pancreatic MIN-6 cells, the glucose-induced movements of karyopherin alpha2 and the stimulation of glucose-induced gene transcription were simultaneously lost between passages 28 and 33. Thus, extracellular glucose regulates a nuclear transport pathway by increasing the nuclear efflux and shuttling of karyopherin alpha2 in cells in which glucose can stimulate the transcription of sugar-responsive genes.
authors.affiliation: Inserm U505, UPMC and Service commun d'imagerie cellulaire IFR58,15 rue de l'Ecole de Médecine, F-75006 Paris, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Cassany
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Guillemain
authors.forename: Christophe
authors.initials: C
authors.lastname: Klein
authors.forename: Véronique
authors.initials: V
authors.lastname: Dalet
authors.forename: Edith
authors.initials: E
authors.lastname: Brot-Laroche
authors.forename: Armelle
authors.initials: A
authors.lastname: Leturque
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D019319:Okadaic Acid / Q000378:metabolism; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D011993:Recombinant Fusion Proteins; D028901:alpha Karyopherins; C087978:karyopherin alpha 2; D019319:Okadaic Acid; D005947:Glucose