title: LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis.
abstract: Defective catabolite export from lysosomes results in lysosomal storage diseases in humans. Mutations in the cystine transporter gene CTNS cause cystinosis, but other lysosomal amino acid transporters are poorly characterized at the molecular level. Here, we identified the Caenorhabditis elegans lysosomal lysine/arginine transporter LAAT-1. Loss of laat-1 caused accumulation of lysine and arginine in enlarged, degradation-defective lysosomes. In mutants of ctns-1 (C. elegans homolog of CTNS), LAAT-1 was required to reduce lysosomal cystine levels and suppress lysosome enlargement by cysteamine, a drug that alleviates cystinosis by converting cystine to a lysine analog. LAAT-1 also maintained availability of cytosolic lysine/arginine during embryogenesis. Thus, LAAT-1 is the lysosomal lysine/arginine transporter, which suggests a molecular explanation for how cysteamine alleviates a lysosomal storage disease.
authors: Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors: Bin
authors: B
authors: Liu
authors: Hongwei
authors: H
authors: Du
authors: Rachael
authors: R
authors: Rutkowski
authors: Anton
authors: A
authors: Gartner
authors: Xiaochen
authors: X
authors: Wang
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003543:Cysteamine / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D016464:Lysosomal Storage Diseases / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*
chemical_list: D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D029742:Caenorhabditis elegans Proteins; C573924:LAAT-1 protein, C elegans; C573925:SLC66A1 protein, human; C573923:ctns-1 protein, C elegans; D003543:Cysteamine; D001120:Arginine; D008239:Lysine