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Fig. 9. The complex biology of PGI/AMF and its receptor. At neutral pH, PGI/AMF binds its receptor AMFR at the cell surface and can be endocytosed via two different pathways: caveolae/raft-dependent endocytosis to the smooth ER (1) or clathrin-dependent endocytosis to multivesicular bodies (MVBs) (2). Internalized PGI/AMF can recycle from MVBs to the plasma membrane (3) where it can undergo further rounds of endocytosis and recycling (4). Recycling receptor-ligand complexes can also be sequestered via stable association with FN fibrils (5). PGI/AMF can also interact directly with IGFBP-3 (6), an interaction that reduces its cellular binding. At acid pH, endocytosis is inhibited and PGI/AMF binds directly to FN fibrils (7) or to heparan sulphate (HS) (8).





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