y(+)-type cationic amino acid transport: expression and regulation of the mCAT genes

The transport of cationic amino acids across animal cell membranes is largely mediated by a small group of well-described transport system (y+, bo,+, Bo,+). Only recently have genes encoding transport proteins in some of these systems been isolated. Two genes, mCAT-1 and mCAT-2, encode related multiple membrane-spanning proteins that share substantial amino acid sequence identity and virtually superimposable hydrophilicity profiles. mCAT-1 and mCAT-2 proteins expressed in Xenopus oocytes are functionally indistinguishable and similar to transport system y+, but have distinct tissue distribution patterns. mCAT-1 expression is nearly ubiquitous and produces a single protein, while mCAT-2 is highly tissue-specific, has two distinct protein isoforms encoded by a single gene and is expressed in different tissues using at least two widely separated promoters. All three proteins facilitate the ion-independent transport of arginine, lysine and ornithine. Both mCAT-1 and mCAT-2 proteins have low amino acid sequence similarity but strikingly similar hydrophilicity profiles with amino acid antiporters, uniporters and symporters of yeast, fungi and eubacteria. Current work will elucidate whether any of the mCAT proteins interact with members of a newly identified family of single membrane-spanning proteins, such as rBAT, 4F2 and NAA-Tr, which are thought to modulate or activate y+L and/or bo,+ transport systems.