A di-leucine-based motif in the cytoplasmic tail of LIMP-II and tyrosinase mediates selective binding of AP-3.
Among the various coats involved in vesicular transport, the clathrin associated coats that contain the adaptor complexes AP-1 and AP-2 are the most extensively characterized. The function of the recently described adaptor complex AP-3, which is similar to AP-1 and AP-2 in protein composition but does not associate with clathrin, is not known. By monitoring surface plasmon resonance we observed that AP-3 is able to interact with the tail of the lysosomal integral membrane protein LIMP-II and that this binding depends on a DEXXXLI sequence in the LIMP-II tail. Furthermore, AP-3 bound to the cytoplasmic tail of the melanosome-associated protein tyrosinase which contains a related EEXXXLL sequence. The tails of LIMP-II and tyrosinase either did not interact, or only interacted poorly, with AP-1 or AP-2. In contrast, the cytoplasmic tails of other membrane proteins containing di-leucine and/or tyrosine-based sorting signals did not bind AP-3, but AP-1 and/or AP-2. This points to a function of AP-3 in intracellular sorting to lysosomes and melanosomes of a subset of cargo proteins via di-leucine-based sorting motifs.
Höning
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Institute for Biochemistry II, University of Göttingen, Gosslerstr. 12d, 37073 Göttingen, Germany.
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von Figura
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D000135:Acid Phosphatase / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015374:Biosensing Techniques; D001921:Brain; D018955:CD36 Antigens / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism; D008544:Melanocytes / Q000201:enzymology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D013552:Swine
D033942:Adaptor Proteins, Vesicular Transport; D015703:Antigens, CD; D018955:CD36 Antigens; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D010750:Phosphoproteins; C439023:clathrin assembly protein AP180; D014442:Monophenol Monooxygenase; D000135:Acid Phosphatase; D007930:Leucine