A di-leucine-based motif in the cytoplasmic tail of LIMP-II and tyrosinase mediates selective binding of AP-3

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Abstract
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.