Article: article from journal or magazin.
The tyrosine-based lysosomal targeting signal in lamp-1 mediates sorting into Golgi-derived clathrin-coated vesicles.
Publication types: Journal Article ;
Diversion of membrane proteins from the trans-Golgi network (TGN) or the plasma membrane into the endosomal system occurs via clathrin-coated vesicles (CCVs). These sorting events may require the interaction of cytosolic domain signals with clathrin adaptor proteins (APs) at the TGN (AP-1) or the plasma membrane (AP-2). While tyrosine- and di-leucine-based signals in several proteins mediate endocytosis via cell surface CCVs, segregation into Golgi-derived CCVs has so far only been documented for the mannose 6-phosphate receptors, where it is thought to require a casein kinase II phosphorylation site adjacent to a di-leucine motif. Although recently tyrosine-based signals have also been shown to interact with the mu chain of AP-1 in vitro, it is not clear if these signals also bind intact AP-1 adaptors, nor if they can mediate sorting of proteins into AP-1 CCVs. Here we show that the cytosolic domain of the lysosomal membrane glycoprotein lamp-1 binds AP-1 and AP-2. Furthermore, lamp-1 is present in AP-1-positive vesicles and tubules in the trans-region on the Golgi complex. AP-1 binding as well as localization to AP-1 CCVs require the presence of the functional tyrosine-based lysosomal targeting signal of lamp-1. These results indicate that lamp-1 can exit the TGN in CCVs and that tyrosine signals can mediate these sorting events.
Adaptor Protein Complex alpha Subunits, Adaptor Proteins, Vesicular Transport, Animals, Antigens, CD/analysis, Antigens, CD/metabolism, Biological Transport, Brain Chemistry, Cell Line, Coated Vesicles/chemistry, Coated Vesicles/metabolism, Cytosol, Dogs, Endosomes/metabolism, Golgi Apparatus/metabolism, Intracellular Membranes/chemistry, Lysosome-Associated Membrane Glycoproteins, Lysosomes/metabolism, Membrane Glycoproteins/analysis, Membrane Glycoproteins/metabolism, Membrane Proteins/analysis, Membrane Proteins/metabolism, Mutation, Peptides/chemical synthesis, Peptides/metabolism, Protein Binding, Swine, Tyrosine/physiology
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