Amino acid transporters: roles in amino acid sensing and signalling in animal cells

Abstract

Amino acid availability regulates cellular physiology by modulating gene expression and signal transduction pathways. However, although the signalling intermediates between nutrient availability and altered gene expression have become increasingly well documented, how eukaryotic cells sense the presence of either a nutritionally rich or deprived medium is still uncertain. From recent studies it appears that the intracellular amino acid pool size is particularly important in regulating translational effectors, thus, regulated transport of amino acids across the plasma membrane represents a means by which the cellular response to amino acids could be controlled. Furthermore, evidence from studies with transportable amino acid analogues has demonstrated that flux through amino acid transporters may act as an initiator of nutritional signalling. This evidence, coupled with the substrate selectivity and sensitivity to nutrient availability classically associated with amino acid transporters, plus the recent discovery of transporter-associated signalling proteins, demonstrates a potential role for nutrient transporters as initiators of cellular nutrient signalling. Here, we review the evidence supporting the idea that distinct amino acid "receptors" function to detect and transmit certain nutrient stimuli in higher eukaryotes. In particular, we focus on the role that amino acid transporters may play in the sensing of amino acid levels, both directly as initiators of nutrient signalling and indirectly as regulators of external amino acid access to intracellular receptor/signalling mechanisms.

Acidosis-Sensing Glutamine Pump SNAT2 Determines Amino Acid Levels and Mammalian Target of Rapamycin Signalling to Protein Synthesis in L6 Muscle Cells

“…Signaling effects through amino acid transporters are now a well-established concept in mammalian cell biology (36). Although much remains to be learned about signaling pathways that are affected by SNAT2, the data in Figures 6 and 7 suggest that the level of SNAT2 inhibition by acidosis exerts functionally significant effects on mTOR, consistent with an earlier report of coregulation of SNAT2 and mTOR in L6 cells that were treated with ceramide (17).…”

“…At first glance, this is surprising because a wide range of amino acid transporter genes are expressed in muscle and a number of these transport l-Gln (36). Not all of these, however, directly accumulate l-Gln inside cells against its concentration gradient.…”

“…Not all of these, however, directly accumulate l-Gln inside cells against its concentration gradient. For example, ASC transporters (slc1 A4 and A5) and System L transporters (slc7 A5 and A8) are primarily amino acid exchangers (36) and consequently have only secondary effects on intracellular l-Gln concentration. Transporters of the SNAT/ slc38 family other than SNAT2 can transport l-Gln against a gradient (19) but are unlikely to contribute to l-Gln accumulation in L6 cells because they are expressed only at low level ( Figure 4A).…”

Growth of embryo and gene expression of nutrient transporters in the small intestine of the domestic pigeon (Columba livia)

“…According to Poncet and Taylor (2013), different nutrient transporters have different gene expression patterns and functions. For example, amino acids are transported into the intestinal epithelial cells as di-or tri-peptides by the H + -dependent peptide transporter 1, PepT1 (Leibach and Ganapathy, 1996) or a variety of amino acid transporters that have specificity for anionic, cationic, or neutral amino acids (Hyde et al, 2003). Most of the studies are focused on the gene expressions of intestine nutrient transporters in precocial poultry, such as chicken (Mott et al, 2008;Sun et al, 2015;Miska et al, 2014) and turkey (de Oliveira et al, 2009).…”

<small>L</small>-Lysine Attenuates Hepatic Steatosis in Senescence-Accelerated Mouse Prone 8 Mice

“…It was reported that the mRNA expression level of cationic amino acid transporter (CAT-1) in the liver is increased by intake of Lys in pigs (39), and three basic amino acids (Lys, Arg, and His) are commonly transported via CAT-1 (40). Additionally, His is reported to suppress lipogenesis-related genes in the mouse liver (41).…”