title: Tuning the cellular trafficking of the lysosomal peptide transporter TAPL by its N-terminal domain.
abstract: The homodimeric ATP-binding cassette (ABC) transport complex TAPL (transporter associated with antigen processing-like, ABCB9) translocates a broad spectrum of peptides from the cytosol into the lumen of lysosomes. The presence of an extra N-terminal transmembrane domain (TMD0) lacking any sequence homology to known proteins distinguishes TAPL from most other ABC transporters of its subfamily. By dissecting TAPL, we could assign distinct functions to the core complex and TMD0. The core-TAPL complex, composed of six predicted transmembrane helices and a nucleotide-binding domain, is sufficient for peptide transport, showing that the core transport complex is correctly targeted to and assembled in the membrane. Strikingly, in contrast to the full-length transporter, the core translocation complex is targeted preferentially to the plasma membrane. However, TMD0 alone, comprising a putative four transmembrane helix bundle, traffics to lysosomes. Upon coexpression, TMD0 forms a stable non-covalently linked complex with the core translocation machinery and guides core-TAPL into lysosomal compartments. Therefore, TMD0 represents a unique domain, which folds independently and encodes the information for lysosomal targeting. These outcomes are discussed in respect of trafficking, folding and function of TAPL.
authors.affiliation: Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Demirel
authors.forename: Irina
authors.initials: I
authors.lastname: Bangert
authors.forename: Robert
authors.initials: R
authors.lastname: Tampé
authors.forename: Rupert
authors.initials: R
authors.lastname: Abele
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D017510:Protein Folding; D021381:Protein Transport
chemical_list: C412573:ABCB9 protein, human; D018528:ATP-Binding Cassette Transporters