Document Detail

LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis.
MedLine Citation:
PMID:  22822152     Owner:  NLM     Status:  MEDLINE    
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.
Bin Liu; Hongwei Du; Rachael Rutkowski; Anton Gartner; Xiaochen Wang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  337     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-23     Completed Date:  2012-08-02     Revised Date:  2014-08-25    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  351-4     Citation Subset:  IM    
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MeSH Terms
Amino Acid Transport Systems / genetics,  metabolism
Amino Acid Transport Systems, Basic / genetics,  metabolism*
Arginine / metabolism*
COS Cells
Caenorhabditis elegans / genetics,  metabolism*
Caenorhabditis elegans Proteins / genetics,  metabolism*
Cercopithecus aethiops
Cysteamine / metabolism
Lysine / metabolism*
Lysosomal Storage Diseases / genetics,  metabolism
Lysosomes / genetics,  metabolism*
Grant Support
090944//Wellcome Trust; 0909444/Z/09/Z//Wellcome Trust; A4500//Cancer Research UK; C11852/A4500//Cancer Research UK; C11852/A5991//Cancer Research UK
Reg. No./Substance:
0/Amino Acid Transport Systems; 0/Amino Acid Transport Systems, Basic; 0/Caenorhabditis elegans Proteins; 0/LAAT-1 protein, C elegans; 0/PQLC2 protein, human; 0/ctns-1 protein, C elegans; 5UX2SD1KE2/Cysteamine; 94ZLA3W45F/Arginine; K3Z4F929H6/Lysine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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