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The System L1 amino acid transporter (SLC7A5) facilitates nutrient signalling in mouse skeletal muscle in vivo
Author(s) -
Poncet Nadege,
Taylor Peter Maving
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.350.4
Subject(s) - p70 s6 kinase 1 , pi3k/akt/mtor pathway , skeletal muscle , medicine , leucine , endocrinology , amino acid transporter , chemistry , biology , biochemistry , amino acid , signal transduction , transporter , gene
The System L1‐type amino acid transporter (LAT1; catalytic subunit SLC7A5) mediates transport of large neutral amino acids (LNAA) in many mammalian cell‐types. LNAA such as leucine are required for full activation of the mTOR‐S6K signalling pathway promoting protein synthesis and cell growth. We investigated the role of intracellular LNAA delivery by the LAT1 transporter for mTOR‐S6K pathway activation in skeletal muscle using muscle‐specific (MCK Cre‐mediated) SLC7A5 knockout (KO) mice and wild‐type littermates fed for 10 weeks (to age 105 days) with diets of 10, 20 or 30% protein. Food intake and growth rate were similar for all groups. In muscle‐specific SLC7A5‐KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by 35% and Gln increased by 27% (relative to wild‐type) as dietary protein content was reduced from 30 to 10%. These changes were associated with >;50% decrease in S6K Thr 389 phosphorylation in SLC7A5‐KO muscle, indicating reduced mTOR‐S6K pathway activation, despite no difference in lean tissue mass between genotypes on the same diet. SLC7A5 modulates LNAA‐dependent muscle mTOR‐S6K signalling in mice, although it appears non‐essential for maintenance of normal muscle mass.