The leucine-based sorting motifs in the cytoplasmic domain of the invariant chain are recognized by the clathrin adaptors AP1 and AP2 and their medium chains

Recognition of sorting signals within the cytoplasmic tail of membrane prot eins by adaptor protein complexes is a crucial step in membrane protein sor ting. The three known adaptor complexes, AP1, AP2, and AP3, have all been s hown to recognize tyrosine- and leucine-based sorting signals, which are th e most common sorting signals within membrane protein cytoplasmic tails, Al though tyrosine-based signals are recognized by the mu-chains of adaptor co mplexes, the subunit recognizing leucine-based sorting signals is less clea r. In this report we show by surface plasmon resonance that the two leucine -based sorting signals within the cytoplasmic tail of the invariant chain b ind independently from each other to API and AP2 but not to AP3, We also sh ow that both motifs can be recognized by the mu-chains of API and AP2, More over, by using monomeric as well as trimeric invariant chain constructs, we show that adaptor binding does not require trimerization of the invariant chain.