Drosophila expresses a CD98 transporter with evolutionarily conserved structure and amino acid transport properties
Résumé
Mammalian CD98 heterodimeric amino acid transporters consist of a promiscuous single-pass transmembrane glycoprotein, CD98hc, the ‘heavy chain', and one of six multipass transmembrane proteins, or ‘light chains'. The heterodimeric complexes of CD98hc and the light chains LAT1 or LAT2 specifically promote sodium-independent System L exchange of neutral amino acids, including leucine. CD98hc is also implicated in other processes, including cell fusion, cell adhesion and activation of TOR signalling. Recent reports surprisingly suggested that insects lack a membrane-bound CD98hc, but here we show that Drosophila CG2791 encodes a functional CD98hc orthologue with conservation in intracellular, transmembrane and extracellular domains. We demonstrate by RNAi knockdown in DrosophilaSchneider cells that CG2791 and two Drosophilahomologues of the mammalian CD98 light chains, Minidiscs (Mnd) and JhI-21, are required for normal levels of System L transport. Furthermore, we show that System L activity is increased by methoprene, an analogue of the developmentally regulated endocrine hormone, Juvenile Hormone, an effect potentially mediated by elevated Mnd expression. Co-expression of CG2791 and JhI-21, but not CG2791 and Mnd, in Xenopus oocytes mediates System L transport. Finally, mapping of conserved sequences on to the recently determined crystal structure of the human CD98hc extracellular domain highlights two conserved exposed hydrophobic patches at either end of the domain that are potential protein-protein interaction surfaces. Our data therefore not only show that there is functional conservation of CD98hc System L transporters in flies, but also provide new insights into the structure, functions and regulation of heterodimeric amino acid transporters.
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