Premium
The tyrosine‐based lysosomal targeting signal in lamp‐1 mediates sorting into Golgi‐derived clathrin‐coated vesicles.
Author(s) -
Höning S.,
Griffith J.,
Geuze H. J.,
Hunziker W.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00908.x
Subject(s) - biology , microbiology and biotechnology , golgi apparatus , clathrin , endocytosis , endosome , vesicle , tyrosine , tyrosine phosphorylation , signal transducing adaptor protein , protein targeting , phosphorylation , biochemistry , membrane protein , receptor , endoplasmic reticulum , membrane , intracellular
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.