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Uncharged tRNA and Sensing of Amino Acid Deficiency in Mammalian Piriform Cortex
Shuzhen Hao,1
James W. Sharp,1
Catherine M. Ross-Inta,1
Brent J. McDaniel,2
Tracy G. Anthony,2
Ronald C. Wek,3
Douglas R. Cavener,4
Barbara C. McGrath,4
John B. Rudell,1
Thomas J. Koehnle,5
Dorothy W. Gietzen1*
Abstract:
Recognizing a deficiency of indispensable amino acids (IAAs)for protein synthesis is vital for dietary selection in metazoans,including humans. Cells in the brain's anterior piriform cortex(APC) are sensitive to IAA deficiency, signaling diet rejectionand foraging for complementary IAA sources, but the mechanismis unknown. Here we report that the mechanism for recognizingIAA-deficient foods follows the conserved general control (GC)system, wherein uncharged transfer RNA induces phosphorylationof eukaryotic initiation factor 2 (eIF2) via the GC nonderepressing2 (GCN2) kinase. Thus, a basic mechanism of nutritional stressmanagement functions in mammalian brain to guide food selectionfor survival.
1 School of Veterinary Medicine, Department of Anatomy, Physiology and Cell Biology, University of California, Davis, CA 95616, USA. 2 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Evansville, IN 47712, USA. 3 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. 4 Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA. 5 Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
* To whom correspondence should be addressed. E-mail: dwgietzen{at}ucdavis.edu
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