Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex.
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 rejection and foraging for complementary IAA sources, but the mechanism is unknown. Here we report that the mechanism for recognizing IAA-deficient foods follows the conserved general control (GC) system, wherein uncharged transfer RNA induces phosphorylation of eukaryotic initiation factor 2 (eIF2) via the GC nonderepressing 2 (GCN2) kinase. Thus, a basic mechanism of nutritional stress management functions in mammalian brain to guide food selection for survival.
Hao
Shuzhen
S
School of Veterinary Medicine, Department of Anatomy, Physiology and Cell Biology, University of California, Davis, CA 95616, USA.
Sharp
James W
JW
Ross-Inta
Catherine M
CM
McDaniel
Brent J
BJ
Anthony
Tracy G
TG
Wek
Ronald C
RC
Cavener
Douglas R
DR
McGrath
Barbara C
BC
Rudell
John B
JB
Koehnle
Thomas J
TJ
Gietzen
Dorothy W
DW
D000215:Acylation; D000601:Amino Acids, Essential / Q000008:administration & dosage* / Q000032:analysis / Q000172:deficiency*; D000818:Animals; D004032:Diet; D004435:Eating; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D005502:Food; D005518:Food Preferences; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009833:Olfactory Pathways / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D012343:RNA, Transfer / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013912:Threonine / Q000008:administration & dosage; D019892:eIF-2 Kinase / Q000378:metabolism
D000601:Amino Acids, Essential; D015852:Eukaryotic Initiation Factor-2; D007930:Leucine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012343:RNA, Transfer; D013912:Threonine; D019892:eIF-2 Kinase; C417575:leucinol; C070634:Eif2ak4 protein, mouse