AP-4, a novel protein complex related to clathrin adaptors

Here we report the identification and characterization of AP-4, a novel protein complex related to the heterotetrameric AP-1, AP-2, and AP-3 adaptors that mediate protein sorting in the endocytic and late secretory pathways. The key to the identification of this complex was the cloning and sequencing of two widely expressed, mammalian cDNAs encoding new homologs of the adaptor beta and a subunits named beta 4 and sigma 4, respectively. An antibody to beta 4 recognized in human cells an similar to 83-kDa polypeptide that exists in both soluble and membrane-associated forms. Golgi filtration, sedimentation velocity, and immunoprecipitation experiments revealed that beta 4 is a component of a multisubunit complex (AP-4) that also contains the sigma 4 polypeptide and two additional adaptor subunit homologs named mu 4 (mu-ARP2) and epsilon. Immunofluorescence analyses showed that AP-4 is associated with the trans-Golgis network or an adjacent structure and that this association is sensitive to the drug brefeldin A. We propose that, like the related AP-1, AP-2, and AP-3 complexes, AP-4 plays a role in signal-mediated trafficking of integral membrane proteins in mammalian cells.