The mammalian AP-3 adaptor-like complex mediates the intracellular transport of lysosomal membrane glycoproteins.
In mammalian cells, the mannose 6-phosphate receptors (MPRs) and the lysosomal glycoproteins, lysosomal-associated membrane protein (LAMP) I, lysosomal integral membrane protein (LIMP) II, are directly transported from the trans-Golgi network to endosomes and lysosomes. While MPR traffic relies on the AP-1 adaptor complex, we report that proper targeting of LAMP I and LIMP II to lysosomes requires the AP-3 adaptor-like complex. Overexpression of these proteins, which contain either a tyrosine- or a di-leucine-based-sorting motif, promotes AP-3 recruitment on membranes. Inhibition of AP-3 function using antisense oligonucleotides leads to a selective misrouting of both LAMP I and LIMP II to the cell surface without affecting MPR trafficking. These results provide evidence that AP-3 functions in the intracellular targeting of transmembrane glycoproteins to lysosomes.
Le Borgne
R
R
Institut de Biologie de Lille, CNRS EP 525 Institut Pasteur de Lille, BP 447, 59021 Lille Cédex, France.
Alconada
A
A
Bauer
U
U
Hoflack
B
B
D033963:Adaptor Protein Complex 3; D033981:Adaptor Protein Complex delta Subunits; D015703:Antigens, CD / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D004151:Dipeptides / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins; D051116:Receptors, Scavenger; D012795:Sialoglycoproteins; D014157:Transcription Factors / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
C491904:AP3D1 protein, human; D033963:Adaptor Protein Complex 3; D033981:Adaptor Protein Complex delta Subunits; D015703:Antigens, CD; D018955:CD36 Antigens; D017931:DNA Primers; D004151:Dipeptides; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D051116:Receptors, Scavenger; C074299:SCARB2 protein, human; C489452:Scarb2 protein, mouse; D012795:Sialoglycoproteins; D014157:Transcription Factors; D014443:Tyrosine; D007930:Leucine