QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Obermüller, S. Articles by Höning, S. Search for Related Content PubMed PubMed Citation Articles by Obermüller, S. Articles by Höning, S.

The tyrosine motifs of Lamp 1 and LAP determine their direct and indirect targetting to lysosomes

Institute for Biochemistry II, University of Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany

*Address for correspondence (e-mail: shoenin{at}gwdg.de)

Accepted September 21, 2001

Lamp 1 and lysosomal acid phosphatase (LAP) are lysosomal membrane proteins that harbour a tyrosine-based sorting motif within their short cytoplasmic tails. Lamp 1 is delivered from the trans-Golgi network (TGN) via endosomes directly to lysosomes bypassing the plasma membrane, whereas LAP is indirectly transported to lysosomes and recycles between endosomes and the plasma membrane before being delivered to lysosomes.

By analysing truncated forms of LAP and chimeras in which the cytoplasmic tail or part of the cytoplasmic tails of LAP and Lamp 1 were exchanged, we were able to show that the YRHV tyrosine motif of LAP is necessary and sufficient to mediate recycling between endosomes and the plasma membrane. When peptides corresponding to the cytoplasmic tails of LAP and Lamp 1 and chimeric or mutant forms of these tails were assayed for in vitro binding of AP1 and AP2, we found that AP2 bound to LAP- and Lamp-1-derived peptides, whereas AP1 bound only to peptides containing the YQTI tyrosine motif of Lamp 1. Residues +2 and +3 of the tyrosine motif were critical for the differential binding of adaptors. LAP in which these residues (–HV) were substituted for those of Lamp 1 (–TI) was transported directly to lysosomes, whereas a chimera carrying the Lamp 1 tail in which residues +2 and +3 were substituted for those of LAP (–HV) gained the ability to recycle. In conclusion, the residues +2 and +3 of the tyrosine motifs determine the sorting of Lamp 1 and LAP in endosomes, mediating either the direct or the indirect pathway to lysosomes.

Key words: Endosome, Protein sorting, Cytoplasmic tail, Recycling, Clathrin

This article has been cited by other articles:

				Y. Abdul Jalil, V. Ritz, A. Jakimenko, C. Schmitz-Salue, H. Siebert, D. Awuah, A. Kotthaus, T. Kietzmann, C. Ziemann, and K. I. Hirsch-Ernst Vesicular localization of the rat ATP-binding cassette half-transporter rAbcb6 Am J Physiol Cell Physiol, February 1, 2008; 294(2): C579 - C590. [Abstract] [Full Text] [PDF]

				F. B. Guloglu and C. A. J. Roman Precursor B Cell Receptor Signaling Activity Can Be Uncoupled from Surface Expression. J. Immunol., June 1, 2006; 176(11): 6862 - 6872. [Abstract] [Full Text] [PDF]

				F. Tribl, M. Gerlach, K. Marcus, E. Asan, T. Tatschner, T. Arzberger, H. E. Meyer, G. Bringmann, and P. Riederer "Subcellular Proteomics" of Neuromelanin Granules Isolated from the Human Brain Mol. Cell. Proteomics, July 1, 2005; 4(7): 945 - 957. [Abstract] [Full Text] [PDF]

				N. Touret, P. Paroutis, and S. Grinstein The nature of the phagosomal membrane: endoplasmic reticulum versus plasmalemma J. Leukoc. Biol., June 1, 2005; 77(6): 878 - 885. [Abstract] [Full Text] [PDF]

				S. Storch, S. Pohl, and T. Braulke A Dileucine Motif and a Cluster of Acidic Amino Acids in the Second Cytoplasmic Domain of the Batten Disease-related CLN3 Protein Are Required for Efficient Lysosomal Targeting J. Biol. Chem., December 17, 2004; 279(51): 53625 - 53634. [Abstract] [Full Text] [PDF]

				C. Scott, M. E. Higgins, J. P. Davies, and Y. A. Ioannou Targeting of NPC1 to Late Endosomes Involves Multiple Signals, Including One Residing within the Putative Sterol-sensing Domain J. Biol. Chem., November 12, 2004; 279(46): 48214 - 48223. [Abstract] [Full Text] [PDF]

				F. Gaden, L. Franqueville, M. K. Magnusson, S. S. Hong, M. D. Merten, L. Lindholm, and P. Boulanger Gene Transduction and Cell Entry Pathway of Fiber-Modified Adenovirus Type 5 Vectors Carrying Novel Endocytic Peptide Ligands Selected on Human Tracheal Glandular Cells J. Virol., July 1, 2004; 78(13): 7227 - 7247. [Abstract] [Full Text] [PDF]

				E. T. A. Marques Jr., P. Chikhlikar, L. B. de Arruda, I. C. Leao, Y. Lu, J. Wong, J.-S. Chen, B. Byrne, and J. T. August HIV-1 p55Gag Encoded in the Lysosome-associated Membrane Protein-1 as a DNA Plasmid Vaccine Chimera Is Highly Expressed, Traffics to the Major Histocompatibility Class II Compartment, and Elicits Enhanced Immune Responses J. Biol. Chem., September 26, 2003; 278(39): 37926 - 37936. [Abstract] [Full Text] [PDF]

				D. G. Rodionov, S. Honing, A. Silye, T. L. Kongsvik, K. von Figura, and O. Bakke Structural Requirements for Interactions between Leucine-sorting Signals and Clathrin-associated Adaptor Protein Complex AP3 J. Biol. Chem., November 27, 2002; 277(49): 47436 - 47443. [Abstract] [Full Text] [PDF]

				Z. Su, J. Vieweg, A. Z. Weizer, P. Dahm, D. Yancey, V. Turaga, J. Higgins, D. Boczkowski, E. Gilboa, and J. Dannull Enhanced Induction of Telomerase-specific CD4+ T Cells Using Dendritic Cells Transfected with RNA Encoding a Chimeric Gene Product Cancer Res., September 1, 2002; 62(17): 5041 - 5048. [Abstract] [Full Text] [PDF]