Amino acids suppress the expression of PAT 1 on lysosomes via inducing the cleavage of a targeting signal

The lysosome-associated transporter proton-coupled amino acid transporter 1 (PAT1) promotes nutrient recycling through releasing luminal amino acids into the cytosol. Using HEK293 cells expressing an EGFP-tagged PAT1 (EGFP-PAT1) as a model, we identified a consensus tyrosine-based targeting signal in the cytosolic N-terminal region of PAT1, which facilitates its expression on the lysosome. Interestingly, this signal can be removed via protein cleavage in an amino acid-sensitive manner. The cleavage is suppressed upon amino acid starvation and is induced by amino acid replenishment. However, amino acid deficiency does not suppress the cleavage of amino acid-binding mutants of EGFP-PAT1. Our data support a mechanism, whereby amino acid binding induces PAT1 cleavage to remove a targeting signal, thus suppressing the expression of PAT1 on the lysosome.