| LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis. | |
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MedLine Citation:
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PMID: 22822152 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Bin Liu; Hongwei Du; Rachael Rutkowski; Anton Gartner; Xiaochen Wang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 337 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-07-23 Completed Date: 2012-08-02 Revised Date: 2013-04-05 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 351-4 Citation Subset: IM |
Affiliation:
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Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Transport Systems
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genetics,
metabolism Amino Acid Transport Systems, Basic / genetics, metabolism* Animals Arginine / metabolism* COS Cells Caenorhabditis elegans / genetics, metabolism* Caenorhabditis elegans Proteins / genetics, metabolism* Cercopithecus aethiops Cysteamine / metabolism Homeostasis Humans Lysine / metabolism* Lysosomal Storage Diseases / genetics, metabolism Lysosomes / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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090944//Wellcome Trust; 0909444/Z/09/Z//Wellcome Trust; A4500//Cancer Research UK; C11852/A4500//Cancer Research UK; C11852/A5991//Cancer Research UK |
| Chemical | |
Reg. No./Substance:
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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/cystinosin protein, C elegans; 56-87-1/Lysine; 60-23-1/Cysteamine; 74-79-3/Arginine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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