AP‐1 Membrane–Cytoplasm Recycling Regulated by μ1A‐Adaptin

The adaptor protein complex AP‐1 mediates vesicular protein sorting between the trans Golgi network and endosomes. AP‐1 recycles between membranes and the cytoplasm together with clathrin during transport vesicle formation and vesicle uncoating. AP‐1 recycles independent of clathrin, indicating binding to unproductive membrane domains and premature termination of vesicle budding. Membrane recruitment requires ADP ribosylation factor‐1‐GTP, a transmembrane protein containing an AP‐1‐binding motif and phosphatidyl‐inositol phosphate (PI‐4‐P). Little is known about the regulation of AP‐1 membrane–cytoplasm recycling. We identified the N‐terminal domain of μ1A‐adaptin as being involved in the regulation of AP‐1 membrane–cytoplasm recycling by constructing chimeras of μ1A and its homologue μ2. The AP‐1* complex containing this μ2–μ1A chimera had slowed down recycling kinetics, resulting in missorting of mannose 6‐phosphate receptors. The N‐terminal domain is only accessible from the cytoplasmic AP‐1 surface. None of the proteins known to influence AP‐1 membrane recycling bound to this μ1A domain, indicating the regulation of AP‐1 membrane–cytoplasm recycling by an yet unidentified cytoplasmic protein.

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