Evidence for glucose and sorbitol-induced nuclear export of glucokinase regulatory protein in hepatocytes.
Glucokinase is rapidly exported from the nucleus of hepatocytes in response to a rise in glucose or fructose 1-P. We demonstrate using confocal microscopy and quantitative imaging that in contrast to previous findings, the regulatory protein of glucokinase (GKRP) also translocates from the nucleus during substrate-induced translocation of glucokinase. However, the fractional decrease in nuclear GKRP is smaller than for glucokinase and is determined by the metabolic state and not by the distribution of glucokinase. Translocation of glucokinase and GKRP is not inhibited by leptomycin B, an inhibitor of exportin-1 function. These findings highlight the importance of quantitative imaging for determining nuclear export of proteins and suggest that GKRP may have a role in nuclear export or import of glucokinase.
Mukhtar
M
M
Department of Diabetes, University of Newcastle upon Tyne, The Medical School, UK.
Stubbs
M
M
Agius
L
L
D000818:Animals; D002352:Carrier Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004072:Digitonin / Q000493:pharmacokinetics; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005941:Glucokinase / Q000096:biosynthesis / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D013012:Sorbitol / Q000494:pharmacology*; D013997:Time Factors
D002352:Carrier Proteins; D005231:Fatty Acids, Unsaturated; C499484:Gckr protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C080906:glucokinase regulatory protein; D013012:Sorbitol; D005941:Glucokinase; D005947:Glucose; D004072:Digitonin; C038753:leptomycin B