A karyopherin alpha2 nuclear transport pathway is regulated by glucose in hepatic and pancreatic cells.
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.
Cassany
Aurélia
A
Inserm U505, UPMC and Service commun d'imagerie cellulaire IFR58,15 rue de l'Ecole de Médecine, F-75006 Paris, France.
Guillemain
Ghislaine
G
Klein
Christophe
C
Dalet
Véronique
V
Brot-Laroche
Edith
E
Leturque
Armelle
A
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*
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