TRANSPORTERS FOR CATIONIC AMINO-ACIDS IN ANIMAL-CELLS - DISCOVERY, STRUCTURE, AND FUNCTION

The structure and function of the four cationic amino acid transporter s identified in animal cells are discussed. The systems differ in spec ificity, cation dependence, and physiological role. One of them, syste m y(+), is selective for cationic amino acids, whereas the others (B-0 ,B-+, b(0,+) and y(+)L) also accept neutral amino acids. In recent yea rs, cDNA clones related to these activities have been isolated. Thus t wo families of proteins have been identified: 1) CAT or cationic amino acid transporters and 2) BAT or broad-scope transport proteins. In th e CAT family, three genes encode for four different isofonns [CAT-1, C AT-2A, CAT-2CB) and CAT-3]; these are similar to 70-kDa proteins with multiple transmembrane segments (12-14), and despite their structural similarity, they differ in tissue distribution, kinetics, and regulato ry properties. System y(+) is the espression of the actitity of CAT tr ansporters. The BAT family includes two isoforms (rBAT and 4F2hc); the se are 59-to 78-kDa proteins with one to four membrane-spanning segmen ts, and it has been proposed that these proteins act as transport regu lators. The expression of rBAT and 4F2hc induces system b(0,+) and sys tem y(+)L activity in Xenopus laevis oocytes, respectively. The roles of these transporters in nutrition, endocrinology, nitric oxide biolog y, and immunology, as well as in the genetic diseases cystinuria and l ysinuric protein intolerance, are resiewed. Experimental strategies, w hich can be used in the Idnetic characterization of coexpressed transp orters, are also discussed.