A REGION FROM THE MEDIUM-CHAIN ADAPTER SUBUNIT (MU) RECOGNIZES LEUCINE-BASED AND TYROSINE-BASED SORTING SIGNALS

Tyrosine-based sorting signals in the cytosolic tails of membrane prot eins have been found to bind directly to the medium chain subunit (mu) of the adaptor complexes AP-1 and AP-2, For the leucine-based signals , an interaction with AP-1 and AP-2 has been reported, but no specific interacting subunit has been demonstrated. After searching for molecu les interacting with the leucine-based sorting signals within the cyto solic tail of the major histocompatibility complex class II-associated invariant chain using a phage display approach, we identified phage c lones with homology to a conserved region of the AP-1 and AP-2 mu chai ns, To investigate the relevance of these findings, we have expressed regions of mouse mu(1) and mu(2), chains on phage gene product III and investigated the binding to tail sequences from various transmembrane proteins with known endosomal targeting signals, Enzyme-linked immuno sorbent binding assays showed that these phages specifically recognize d peptides containing functional leucine-and tyrosine-based sorting si gnals, suggesting that these regions of the mu(1) and mu(2) chains int eract with both types of sorting signals.