The Mammalian AP-3 Adaptor-like Complex Mediates the Intracellular Transport of Lysosomal Membrane Glycoproteins*
- From the Institut de Biologie de Lille, CNRS EP 525 Institut Pasteur de Lille, BP 447, 59021 Lille Cédex, France
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.
Footnotes
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↵* This work was supported by CNRS, Pasteur Institut, and Grants from the organizations “Vaincre les Maladies Lysosomales” and “Fondation pour la Recherche Medicale.”The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Present address: Biozentrum der Universität Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
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↵§ To whom correspondence should be addressed: Institut de Biologie de Lille, CNRS EP 525, Institut Pasteur de Lille, BP 447, 1, rue Professeur Calmette, 59021 Lille Cédex, France. Tel.: 33 3 20 87 10 25; Fax: 33 3 20 87 10 19; E-mail:Bernard.Hoflack{at}Pasteur-Lille.fr.
- Abbreviations:
- TGN
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trans-Golgi network
- MPR
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mannose 6-phosphate receptor
- LAP
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lysosomal acid phosphatase
- LAMP
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lysosomal-associated membrane protein
- LIMP
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lysosomal integral membrane protein
- VZV
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varicella-zoster virus
- FITC
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fluorescein isothiocyanate
- HA
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hemagglutinin, GTPγS, guanosine 5′-O-(thiotriphosphate).
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- Received August 3, 1998.
- Revision received August 28, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
