Differential topochemistry of three cationic amino acid transporter proteins, hCAT1, hCAT2 and hCAT3, in the adult human brain

Abstract

The cellular uptake of L-arginine and other cationic amino acids (such as L-lysine and L-ornithine) is mainly mediated by cationic amino acid transporter (CAT) proteins. Despite the important roles of cationic amino acid transporters for normal brain functioning and various brain diseases there is currently only fragmentary knowledge about their cellular and regional distribution patterns in the human brain. We mapped the immunohistochemical localization of human cationic amino acid transporters 1, 2 and 3 (hCAT1, 2, and 3) throughout five adult human brains and found a wide but uneven distribution of these transporters. All three hCAT1s were mainly localized in neurons, but were also found in numerous astrocytes, oligodendrocytes, plexus choroideus epithelial cells, and small blood vessels. The highest density of hCAT expressing neurons was observed in the hypothalamus, in some areas of the cerebral cortex, the thalamic reticular nucleus and the caudate nucleus, whereas weak to moderate expression was detected in the hippocampus, the prefrontal cortex (hCAT1 only), pons, brain stem and cerebellum. In contrast to what has been found in rodent brain, we detected hCAT2 and hCAT3 also in astrocytes. Overall, each hCAT has its characteristic, individual cerebral expression patterns, which, however, overlap with the others.

Triple therapy with pyridoxine, arginine supplementation and dietary lysine restriction in pyridoxine-dependent epilepsy: Neurodevelopmental outcome

“…The theoretical basis for this approach is based on the characteristics of the dibasic amino acid transporters. The transport system for cationic amino acids in the brain at the blood-brain barrier as well as in neurons and astrocytes is comprised of mCAT1, encoded by SLC7A1, and mCAT3, encoded by SLC7A3, whereas in the liver it is composed by isoforms of mCTA2, encoded by SLC7A2 [33][34][35]. Both mCAT1 and mCAT3 are sodium-independent transporters with a high affinity for L-arginine, L-lysine, and L-ornithine with a Km in Fig.…”

Hypomorphic variants of cationic amino acid transporter 3 in males with autism spectrum disorders

“…CAT-3 has been reported to be specifically expressed in the brain during embryonic development, suggesting that SLC7A3 plays a role for in brain development, but this finding is controversial (Hosokawa et al 1997 , 1999 ; Ito and Groudine 1997 ; Closs 2002 ; Vekony et al 2001 ; Jager et al 2013 ). We therefore developed a quantitative RT-PCR assay to monitor the expression of CAT-3 in the developing mouse brain.…”

“…The main function of cationic amino acid transporters (CAT) is to mediate the entry of l -type cationic amino acids (i.e., l -arginine, l -ornithine and l -lysine) into many different cell types including neurons (Closs et al 2006 ; Jager et al 2013 ). Their function is crucial since lysine and arginine, under certain conditions, are essential amino acids that are derived exclusively from the degradation of ingested nutrients.…”

SLC Solute Carrier Transporters and Neurodegenerative Disorders: Drawing Attention to Cationic Amino Acid Transporters 1 and 2

“…Both CAT1 and CAT2 are widely expressed in rat and human brain. They are predominantly localized in neurons, but are also found in numerous astrocytes, oligodendrocytes, choroid plexus epithelial cells, and small blood vessels [6][7][8][9]. The second (and even more important) question is: Is there any evidence for an involvement of either CAT1 or CAT2 in neurodegeneration?…”