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

被引:175
作者
Sagné, C
Agulhon, C
Ravassard, P
Darmon, M
Hamon, M
El Mestikawy, S
Gasnier, B
Giros, B
机构
[1] CHU Henri Mondor, INSERM, U513, F-94010 Creteil, France
[2] CHU Pitie Salpetriere, INSERM, U288, F-75634 Paris 13, France
[3] Hop La Pitie Salpetriere, CNRS, UMR 9923, F-75013 Paris, France
[4] CNRS, UPR 1929, Inst Biol Physicochim, F-75005 Paris, France
关键词
D O I
10.1073/pnas.121183498
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 HC-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.
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页码:7206 / 7211
页数:6
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