Regulation of glucose carriers in chick fibroblasts.
The derepression of glucose transport initiated by removing glucose from the incubation medium requires both protein and RNA synthesis. The synthesis and accumulation of putative mRNA for the carrier protein(s) can be demonstrated by inhibiting protein synthesis with cycloheximide (2 microgram/ml). Release from inhibition with simultaneous addition of actinomycin D (1-5 microgram/ml) results in a burst of carrier synthesis that achieves virtually maximal derepression in 4-6 h. An external energy source provided by a "nonrepressive" sugar (D-fructose, D-xylose) or by pyruvate is required to accomplish carrier synthesis. Previous failure to demonstrate mRNA accumulation was due to the depletion of energy in the starved cells. Glucose acts as a repressor at a posttranscriptional step, probably at the level of turnover of formed carrier. The protection of formed carrier in the absence of glucose and by inhibitors of protein synthesis even in the presence of glucose has encouraged conjecture that a protease is activated by a metabolic product of glucose that is analogous to a corepressor. The glucose metabolite either activates the protease by direct interaction with it or alters the conformation of the carrier to expose a critical region to protease attack. Indeed the regulation of carrier density in the membrane of chick fibroblasts may be achieved entirely by carrier inactivation, the rate of which is a function of glucose concentration in the culture medium.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism
D002352:Carrier Proteins; D012333:RNA, Messenger; D003513:Cycloheximide; D005947:Glucose