The lysosomal polypeptide transporter TAPL is stabilized by the interaction with LAMP-1 and LAMP-2

Abstract

TAPL (ABCB9) is a homodimeric polypeptide translocation machinery which transports cytosolic peptides into the lumen of lysosomes for degradation. Since the function of proteins is strongly dependent on the interaction network involved, we investigated the interactome of TAPL. A proteomic approach allowed to identify with lower frequency major histocompatibility complex II subunits and as most abundant interaction partners the lysosome-associated membrane proteins LAMP-1 and LAMP-2B. The interaction site of LAMP was mapped to TMD0 which is a four transmembrane helices comprising N-terminal domain of TAPL. The LAMP proteins bind independently from one another to TAPL. This interaction has neither influence on subcellular localization nor on peptide transport activity. However, in LAMP deficient cells the half-life of TAPL is decreased by a factor of five whereas LIMP-2 as another lysosomal membrane protein is not affected. Reduced stability of TAPL is caused by increased lysosomal degradation indicating that LAMP proteins retain TAPL on the limiting membrane of endosomes and prevent its sorting to intraluminal vesicles.