AP-1 membrane-cytoplasm recycling regulated by μ1A-adaptin

Abstract

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. © 2007 The Authors Journal compilation.