Fig. 1
From: CNMa–CNMa receptor at microbiome–gut–brain axis: novel target to regulate feeding decision
Amino acid-sensing machineries. a During the process of amino acid-driven food selection, the gut communicates with the brain through neurons, secreted hormones and neurotransmitters, and the gut microbiome. In this study, the authors find that gut enterocytes detect and respond to protein limitation through upregulating CNMa expression and communicating with CNMaR-expressing neurons in the brain, leading to the compensatory appetite for L-EAAs. AA, amino acids. b GCN2, an indirect amino acid sensor, could detect any low-level amino acid through binding to the uncharged cognate tRNA, which leads to a conformational change of GCN2. This structural alteration activates the kinase activity of GCN2, culminating in inhibitory phosphorylation of eukaryotic translation initiator factor 2 α (eIF2α) and the increased transcription of starvation-relevant genes, such as activating transcription factor 4 (ATF4). aaRS, aminoacyl transfer RNA synthetase. c TOR is positively regulated by the GTP-charged form of the Ras-like GTPase Rheb (Rheb-GTP) and heterodimeric Rag GTPase. Amino acids deprivation suppresses the kinase activity of TOR through inhibiting the interaction of TOR with the Ras-like GTPase Rheb (Rheb-GTP) and the heterodimeric Rag GTPase.
