RGD Reference Report - Identification and characterization of a lysosomal transporter for small neutral amino acids. - Rat Genome Database

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Identification and characterization of a lysosomal transporter for small neutral amino acids.

Authors: Sagne, C  Agulhon, C  Ravassard, P  Darmon, M  Hamon, M  El Mestikawy, S  Gasnier, B  Giros, B 
Citation: Sagne C, etal., Proc Natl Acad Sci U S A 2001 Jun 19;98(13):7206-11.
RGD ID: 633316
Pubmed: PMID:11390972   (View Abstract at PubMed)
PMCID: PMC34647   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.121183498   (Journal Full-text)

In eukaryotic cells, lysosomes represent a major site for macromolecule degradation. Hydrolysis products are eventually exported from this acidic organelle into the cytosol through specific transporters. Impairment of this process at either the hydrolysis or the efflux step is responsible of several lysosomal storage diseases. However, most lysosomal transporters, although biochemically characterized, remain unknown at the molecular level. In this study, we report the molecular and functional characterization of a lysosomal amino acid transporter (LYAAT-1), remotely related to a family of H+-coupled plasma membrane and synaptic vesicle amino acid transporters. LYAAT-1 is expressed in most rat tissues, with highest levels in the brain where it is present in neurons. Upon overexpression in COS-7 cells, the recombinant protein mediates the accumulation of neutral amino acids, such as gamma-aminobutyric acid, l-alanine, and l-proline, through an H+/amino acid symport. Confocal microscopy on brain sections revealed that this transporter colocalizes with cathepsin D, an established lysosomal marker. LYAAT-1 thus appears as a lysosomal transporter that actively exports neutral amino acids from lysosomes by chemiosmotic coupling to the H+-ATPase of these organelles. Homology searching in eukaryotic genomes suggests that LYAAT-1 defines a subgroup of lysosomal transporters in the amino acid/auxin permease family.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc36a1Ratneutral amino acid transport involved_inIDA PMID:11390972UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc36a1Ratlysosome located_inIDA PMID:11390972UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc36a1Ratneutral L-amino acid transmembrane transporter activity enablesNAS PMID:11390972UniProt 
Slc36a1Ratproton transmembrane transporter activity enablesIDA PMID:11390972UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Slc36a1  (solute carrier family 36 member 1)

Objects referenced in this article
Gene SLC36A1 solute carrier family 36 member 1 Homo sapiens

Additional Information