Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy

摘要

Transport of solute across membranes is crucial to eukary-otic cell physiology, as illustrated by diverse diseases associated with defective transport and the presence of ~400 solute transporter genes in humans. However, the function of many putative transporters remains unknown, such as the proteins responsible for lysosomal export of metabolites. Cystinosin, the lysosomal cystine exporter defective in cystinosis (1), is characterized by a duplicated motif termed the PQ loop. PQ-loop proteins are more frequent in eukaryotes than in prokaryotes, and, except for cystinosin, their molecular function remains unknown. The substrate-coupled proton-binding site is nested in the second PQ loop, suggesting that these motifs have functional significance (2). Here, we showed that another PQ-loop protein, PQLC2, is a lysosomal amino acid transporter that is relevant for the treatment of cystinosis.