AP-1A and AP-3A lysosomal sorting functions.
Heterotetrameric adaptor-protein complexes AP-1A and AP-3A mediate protein sorting in post-Golgi vesicular transport. AP-1A and AP-3A have been localized to the trans-Golgi network, indicating a function in protein sorting at this compartment. AP-3A appears to mediate trans-Golgi network-to-lysosome and also endosome-to-lysosome protein sorting. AP-1A is thought to be required for both trans-Golgi network-to-endosome transport and endosome-to-trans-Golgi network transport. However, the recent discovery of a role for monomeric GGA (Golgi localized gamma-ear containing, ARF binding protein) adaptor proteins in trans-Golgi network to endosome protein transport has brought into question the long-discussed trans-Golgi network-to-endosome sorting function of AP-1A. Murine cytomegalovirus gp48 contains an unusual di-leucine-based lysosome sorting signal motif and mediates lysosomal sorting of gp48/major histocompatibility complex class I receptor complexes, preventing exposure of major histocompatibility complex class I at the plasma membrane. We analyzed lysosomal sorting of gp48/major histocompatibility complex class I receptor complexes in cell lines deficient for AP-1A, AP-3A and both, to determine their sorting functions. We find that AP1-A and AP3-A mediate distinct and sequential steps in the lysosomal sorting. Both sorting functions are required to prevent MHC class I exposure at the plasma membrane at steady-state.
Reusch
Uwe
U
Zentrum für Biochemie and Molekulare Zellbiologie, Department of Biochemie II, Universität Göttingen, Heinrich-Düker-Weg 12, D-37073 Göttingen, Germany.
Bernhard
Olaf
O
Koszinowski
Ulrich
U
Schu
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism; D006868:Hydrolysis; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data
D015395:Histocompatibility Antigens Class I