Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Protein Complex 3
-
Adaptor Protein Complex delta Subunits
-
Antigens, CD / metabolism*
-
Base Sequence
-
Binding Sites
-
Biological Transport
-
CD36 Antigens / metabolism
-
Cell Line
-
DNA Primers
-
Dipeptides / metabolism
-
Endocytosis
-
Humans
-
Intracellular Membranes / metabolism
-
Leucine / metabolism
-
Lysosomal Membrane Proteins
-
Lysosomes / metabolism*
-
Membrane Glycoproteins / metabolism*
-
Membrane Proteins*
-
Receptors, Scavenger
-
Sialoglycoproteins*
-
Transcription Factors / metabolism*
-
Tyrosine / metabolism
Substances
-
AP3D1 protein, human
-
Adaptor Protein Complex 3
-
Adaptor Protein Complex delta Subunits
-
Antigens, CD
-
CD36 Antigens
-
DNA Primers
-
Dipeptides
-
Lysosomal Membrane Proteins
-
Membrane Glycoproteins
-
Membrane Proteins
-
Receptors, Scavenger
-
SCARB2 protein, human
-
Scarb2 protein, mouse
-
Sialoglycoproteins
-
Transcription Factors
-
Tyrosine
-
Leucine