PMID:9412467

Citation	Liu, G, Thomas, L, Warren, RA, Enns, CA, Cunningham, CC, Hartwig, JH and Thomas, G (1997) Cytoskeletal protein ABP-280 directs the intracellular trafficking of furin and modulates proprotein processing in the endocytic pathway. J. Cell Biol. 139:1719-33
Abstract	Furin catalyzes the proteolytic maturation of many proproteins within the trans-Golgi network (TGN)/endosomal system. Furin's cytosolic domain (cd) directs both the compartmentalization to and transit between its manifold processing compartments (i.e., TGN/biosynthetic pathway, cell surface, and endosomes). Here we report the identification of the first furin cd sorting protein, ABP-280 (nonmuscle filamin), an actin gelation protein. The furin cd was used as bait in a yeast two-hybrid screen to identify ABP-280 as a furin-binding protein. Binding analyses in vitro and coimmunoprecipitation studies in vivo showed that furin and ABP-280 interact directly and that ABP-280 tethers furin molecules to the cell surface. Quantitative analysis of both ABP-280-deficient and genetically replete cells showed that ABP-280 modulates the rate of internalization of furin but not of the transferrin receptor, a cycling receptor. However, although ABP-280 directs the rate of furin internalization, the efficiency of sorting of the endoprotease from the cell surface to early endosomes is independent of expression of ABP-280. By contrast, efficient sorting of furin from early endosomes to the TGN requires expression of ABP-280. In addition, ABP-280 is also required for the correct localization of late endosomes (dextran bead uptake) and lysosomes (LAMP-1 staining), demonstrating a pleiotropic role for this actin binding protein in the organization of cellular compartments and directing protein traffic. Finally, and consistent with the trafficking studies on furin, we showed that ABP-280 modulates the processing of furin substrates in the endocytic but not the biosynthetic pathways. The novel roles of ABP-280 and the cytoskeleton in the sorting of furin in the TGN/ endosomal system and the formation of proprotein processing compartments are discussed.
Links	PubMed PMC1424222
Keywords	Amino Acid Sequence; Animals; Base Sequence; Carrier Proteins/metabolism; Cell Compartmentation; Cell Line; Cell Membrane/metabolism; Cercopithecus aethiops; Contractile Proteins/metabolism; Endocytosis; Endosomes/metabolism; Furin; Humans; Lysosomes/metabolism; Microfilament Proteins/metabolism; Models, Biological; Molecular Sequence Data; Protein Precursors/metabolism; Protein Processing, Post-Translational; Receptors, Transferrin/metabolism; Subtilisins/metabolism; Tumor Cells, Cultured
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