Cathepsin S Controls the Trafficking and Maturation of Mhc Class II Molecules in Dendritic Cells

doi:10.1083/jcb.147.4.775

This Article

	Full Text
	Full Text (PDF, 487K)
	PPT slides of all figures
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Driessen, C.
	Articles by Ploegh, H. L.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Driessen, C.
	Articles by Ploegh, H. L.


Social Bookmarking

	What's this?

© The Rockefeller University Press, 0021-9525/1999//775 $5.00
The Journal of Cell Biology, Volume 147, Number 4, , 1999 775-790

Original Article

Cathepsin S Controls the Trafficking and Maturation of Mhc Class II Molecules in Dendritic Cells

Christoph Driessen^a, Rebecca A.R. Bryant^a, Ana-Maria Lennon-Duménil^a, José A. Villadangos^a, Paula Wolf Bryant^a, Guo-Ping Shi^b, Harold A. Chapman^b, and Hidde L. Ploegh^a

^a Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115
^b Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115
Department of Pathology, Harvard Medical School, Building D2, 200 Longwood Ave., Boston, MA 02115.(617) 432-4775(617) 432-4776

ploegh{at}mit.edu

Before a class II molecule can be loaded with antigenic materialand reach the surface to engage CD4+ T cells, its chaperone,the class II-associated invariant chain (Ii), is degraded ina stepwise fashion by proteases in endocytic compartments. Wehave dissected the role of cathepsin S (CatS) in the traffickingand maturation of class II molecules by combining the use ofdendritic cells (DC) from CatS^–/– mice with a newactive site–directed probe for direct visualization ofactive CatS. Our data demonstrate that CatS is active alongthe entire endocytic route, and that cleavage of the lysosomalsorting signal of Ii by CatS can occur there in mature DC. Geneticdisruption of CatS dramatically reduces the flow of class IImolecules to the cell surface. In CatS^–/– DC, thebulk of major histocompatibility complex (MHC) class II moleculesis retained in late endocytic compartments, although paradoxically,surface expression of class II is largely unaffected. The greatlydiminished but continuous flow of class II molecules to thecell surface, in conjunction with their long half-life, canaccount for the latter observation. We conclude that in DC,CatS is a major determinant in the regulation of intracellulartrafficking of MHC class II molecules.

Key Words: major histocompatibility complex class II • cathepsins • dendritic cells • antigen presentation • biological transport

J.A. Villadangos's present address is The Walter and Eliza HallInstitute, Royal Melbourne Hospital, Victoria 3050, Australia.

Abbreviations used in this paper: APC, antigen-presenting cell;CatS, cathepsin S; DC, dendritic cell(s); GM-CSF, granulocyte/macrophagecolony-stimulating factor; Ii, class II-associated invariantchain; LAMP, lysosomal-associated membrane protein; LHVS, N-morpholinurea-homophenylalanyl-leucyl-vinylsulfonemethyl;M6PR, mannose-6-phosphate receptor; MHC, major histocompatibilitycomplex; PDI, protein-disulfide isomerase; PhOH, phenol; PM,plasma membrane; PNS, postnuclear supernatant(s); TfR, transferrinreceptor; wt, wild-type.

CiteULike

Complore

Connotea

Del.icio.us Add to Digg

Digg

Facebook

Technorati

Twitter What's this?

This article has been cited by other articles:

Yu, B., Fonseca, D. P. A. J., O'Rourke, S. M., Berman, P. W. (2010). Protease Cleavage Sites in HIV-1 gp120 Recognized by Antigen Processing Enzymes Are Conserved and Located at Receptor Binding Sites. J. Virol. 84: 1513-1526 [Abstract] [Full Text]
Kasai, M., Tanida, I., Ueno, T., Kominami, E., Seki, S., Ikeda, T., Mizuochi, T. (2009). Autophagic Compartments Gain Access to the MHC Class II Compartments in Thymic Epithelium. J. Immunol. 183: 7278-7285 [Abstract] [Full Text]
Ocana-Morgner, C., Wahren, C., Jessberger, R. (2009). SWAP-70 regulates RhoA/RhoB-dependent MHCII surface localization in dendritic cells. Blood 113: 1474-1482 [Abstract] [Full Text]
de Nooijer, R., Bot, I., von der Thusen, J.H., Leeuwenburgh, M.A., Overkleeft, H.S., Kraaijeveld, A.O., Dorland, R., van Santbrink, P.J., van Heiningen, S.H., Westra, M.M., Kovanen, P.T., Jukema, J.W., van der Wall, E.E., van Berkel, Th.J.C., Shi, G.P., Biessen, E.A.L. (2009). Leukocyte Cathepsin S Is a Potent Regulator of Both Cell and Matrix Turnover in Advanced Atherosclerosis. Arterioscler. Thromb. Vasc. Bio. 29: 188-194 [Abstract] [Full Text]
Lutzner, N., Kalbacher, H. (2008). Quantifying Cathepsin S Activity in Antigen Presenting Cells Using a Novel Specific Substrate. J. Biol. Chem. 283: 36185-36194 [Abstract] [Full Text]
Faure-Andre, G., Vargas, P., Yuseff, M.-I., Heuze, M., Diaz, J., Lankar, D., Steri, V., Manry, J., Hugues, S., Vascotto, F., Boulanger, J., Raposo, G., Bono, M.-R., Rosemblatt, M., Piel, M., Lennon-Dumenil, A.-M. (2008). Regulation of Dendritic Cell Migration by CD74, the MHC Class II-Associated Invariant Chain. Science 322: 1705-1710 [Abstract] [Full Text]
Kessler, T., Reich, M., Jahn, G., Tolosa, E., Beck, A., Kalbacher, H., Overkleeft, H., Schempp, S., Driessen, C. (2008). Human cytomegalovirus infection interferes with major histocompatibility complex type II maturation and endocytic proteases in dendritic cells at multiple levels. J. Gen. Virol. 89: 2427-2436 [Abstract] [Full Text]
Nepal, R. M., Vesosky, B., Turner, J., Bryant, P. (2008). DM, but not cathepsin L, is required to control an aerosol infection with Mycobacterium tuberculosis. J. Leukoc. Biol. 84: 1011-1018 [Abstract] [Full Text]
Kraus, M., Malenke, E., Gogel, J., Muller, H., Ruckrich, T., Overkleeft, H., Ovaa, H., Koscielniak, E., Hartmann, J. T., Driessen, C. (2008). Ritonavir induces endoplasmic reticulum stress and sensitizes sarcoma cells toward bortezomib-induced apoptosis. Molecular Cancer Therapeutics 7: 1940-1948 [Abstract] [Full Text]
Pinto, A. K., Jamieson, A. M., Raulet, D. H., Hill, A. B. (2007). The Role of NKG2D Signaling in Inhibition of Cytotoxic T-Lymphocyte Lysis by the Murine Cytomegalovirus Immunoevasin m152/gp40. J. Virol. 81: 12564-12571 [Abstract] [Full Text]
Kakehashi, H., Nishioku, T., Tsukuba, T., Kadowaki, T., Nakamura, S., Yamamoto, K. (2007). Differential Regulation of the Nature and Functions of Dendritic Cells and Macrophages by Cathepsin E. J. Immunol. 179: 5728-5737 [Abstract] [Full Text]
Le Roux, D., Lankar, D., Yuseff, M.-I., Vascotto, F., Yokozeki, T., Faure-Andre, G., Mougneau, E., Glaichenhaus, N., Manoury, B., Bonnerot, C., Lennon-Dumenil, A.-M. (2007). Syk-dependent Actin Dynamics Regulate Endocytic Trafficking and Processing of Antigens Internalized through the B-Cell Receptor. Mol. Biol. Cell 18: 3451-3462 [Abstract] [Full Text]
Majlessi, L., Combaluzier, B., Albrecht, I., Garcia, J. E., Nouze, C., Pieters, J., Leclerc, C. (2007). Inhibition of Phagosome Maturation by Mycobacteria Does Not Interfere with Presentation of Mycobacterial Antigens by MHC Molecules. J. Immunol. 179: 1825-1833 [Abstract] [Full Text]
Reich, M., van Swieten, P. F., Sommandas, V., Kraus, M., Fischer, R., Weber, E., Kalbacher, H., Overkleeft, H. S., Driessen, C. (2007). Endocytosis targets exogenous material selectively to cathepsin S in live human dendritic cells, while cell-penetrating peptides mediate nonselective transport to cysteine cathepsins. J. Leukoc. Biol. 81: 990-1001 [Abstract] [Full Text]
Vascotto, F., Lankar, D., Faure-Andre, G., Vargas, P., Diaz, J., Le Roux, D., Yuseff, M.-I., Sibarita, J.-B., Boes, M., Raposo, G., Mougneau, E., Glaichenhaus, N., Bonnerot, C., Manoury, B., Lennon-Dumenil, A.-M. (2007). The actin-based motor protein myosin II regulates MHC class II trafficking and BCR-driven antigen presentation. JCB 176: 1007-1019 [Abstract] [Full Text]
Pinto, A. K., Munks, M. W., Koszinowski, U. H., Hill, A. B. (2006). Coordinated Function of Murine Cytomegalovirus Genes Completely Inhibits CTL Lysis.. J. Immunol. 177: 3225-3234 [Abstract] [Full Text]
Wang, Y., Baron, R. M., Zhu, G., Joo, M., Christman, J. W., Silverman, E. S., Perrella, M. A., Riese, R. J., Cernadas, M. (2006). PU.1 Regulates Cathepsin S Expression in Professional APCs. J. Immunol. 176: 275-283 [Abstract] [Full Text]
Rosales-Reyes, R., Alpuche-Aranda, C., Ramirez-Aguilar, M. d. l. L., Castro-Eguiluz, A. D., Ortiz-Navarrete, V. (2005). Survival of Salmonella enterica Serovar Typhimurium within Late Endosomal-Lysosomal Compartments of B Lymphocytes Is Associated with the Inability To Use the Vacuolar Alternative Major Histocompatibility Complex Class I Antigen-Processing Pathway. Infect. Immun. 73: 3937-3944 [Abstract] [Full Text]
Maehr, R., Hang, H. C., Mintern, J. D., Kim, Y.-M., Cuvillier, A., Nishimura, M., Yamada, K., Shirahama-Noda, K., Hara-Nishimura, I., Ploegh, H. L. (2005). Asparagine Endopeptidase Is Not Essential for Class II MHC Antigen Presentation but Is Required for Processing of Cathepsin L in Mice. J. Immunol. 174: 7066-7074 [Abstract] [Full Text]
Dugast, M., Toussaint, H., Dousset, C., Benaroch, P. (2005). AP2 Clathrin Adaptor Complex, but Not AP1, Controls the Access of the Major Histocompatibility Complex (MHC) Class II to Endosomes. J. Biol. Chem. 280: 19656-19664 [Abstract] [Full Text]
Yu, G.-Y., Lai, M. M. C. (2005). The Ubiquitin-Proteasome System Facilitates the Transfer of Murine Coronavirus from Endosome to Cytoplasm during Virus Entry. J. Virol. 79: 644-648 [Abstract] [Full Text]
Lautwein, A., Kraus, M., Reich, M., Burster, T., Brandenburg, J., Overkleeft, H. S., Schwarz, G., Kammer, W., Weber, E., Kalbacher, H., Nordheim, A., Driessen, C. (2004). Human B lymphoblastoid cells contain distinct patterns of cathepsin activity in endocytic compartments and regulate MHC class II transport in a cathepsin S-independent manner. J. Leukoc. Biol. 75: 844-855 [Abstract] [Full Text]
Wilson, N. S., El-Sukkari, D., Villadangos, J. A. (2004). Dendritic cells constitutively present self antigens in their immature state in vivo and regulate antigen presentation by controlling the rates of MHC class II synthesis and endocytosis. Blood 103: 2187-2195 [Abstract] [Full Text]
El-Sukkari, D., Wilson, N. S., Hakansson, K., Steptoe, R. J., Grubb, A., Shortman, K., Villadangos, J. A. (2003). The Protease Inhibitor Cystatin C Is Differentially Expressed among Dendritic Cell Populations, but Does Not Control Antigen Presentation. J. Immunol. 171: 5003-5011 [Abstract] [Full Text]
Kocks, C., Maehr, R., Overkleeft, H. S., Wang, E. W., Iyer, L. K., Lennon-Dumenil, A.-M., Ploegh, H. L., Kessler, B. M. (2003). Functional Proteomics of the Active Cysteine Protease Content in Drosophila S2 Cells. Mol. Cell. Proteomics 2: 1188-1197 [Abstract] [Full Text]
Flannery, T., Gibson, D., Mirakhur, M., McQuaid, S., Greenan, C., Trimble, A., Walker, B., McCormick, D., Johnston, P. G. (2003). The Clinical Significance of Cathepsin S Expression in Human Astrocytomas. Am. J. Pathol. 163: 175-182 [Abstract] [Full Text]
Ackerman, A. L., Cresswell, P. (2003). Regulation of MHC Class I Transport in Human Dendritic Cells and the Dendritic-Like Cell Line KG-1. J. Immunol. 170: 4178-4188 [Abstract] [Full Text]
Kessler, B., Hong, X., Petrovic, J., Borodovsky, A., Dantuma, N. P., Bogyo, M., Overkleeft, H. S., Ploegh, H., Glas, R. (2003). Pathways Accessory to Proteasomal Proteolysis Are Less Efficient in Major Histocompatibility Complex Class I Antigen Production. J. Biol. Chem. 278: 10013-10021 [Abstract] [Full Text]
Greiner, A., Lautwein, A., Overkleeft, H. S., Weber, E., Driessen, C. (2003). Activity and subcellular distribution of cathepsins in primary human monocytes. J. Leukoc. Biol. 73: 235-242 [Abstract] [Full Text]
Felbor, U., Kessler, B., Mothes, W., Goebel, H. H., Ploegh, H. L., Bronson, R. T., Olsen, B. R. (2002). Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc. Natl. Acad. Sci. USA 99: 7883-7888 [Abstract] [Full Text]
Lorenzo, M. E., Jung, J. U., Ploegh, H. L. (2002). Kaposi's Sarcoma-Associated Herpesvirus K3 Utilizes the Ubiquitin-Proteasome System in Routing Class I Major Histocompatibility Complexes to Late Endocytic Compartments. J. Virol. 76: 5522-5531 [Abstract] [Full Text]
Dickinson, D.P. (2002). CYSTEINE PEPTIDASES OF MAMMALS: THEIR BIOLOGICAL ROLES AND POTENTIAL EFFECTS IN THE ORAL CAVITY AND OTHER TISSUES IN HEALTH AND DISEASE. CROBM 13: 238-275 [Abstract] [Full Text]
Storm van's Gravesande, K., Layne, M. D., Ye, Q., Le, L., Baron, R. M., Perrella, M. A., Santambrogio, L., Silverman, E. S., Riese, R. J. (2002). IFN Regulatory Factor-1 Regulates IFN-{gamma}-Dependent Cathepsin S Expression. J. Immunol. 168: 4488-4494 [Abstract] [Full Text]
Hsieh, C.-S., deRoos, P., Honey, K., Beers, C., Rudensky, A. Y. (2002). A Role for Cathepsin L and Cathepsin S in Peptide Generation for MHC Class II Presentation. J. Immunol. 168: 2618-2625 [Abstract] [Full Text]
Lankar, D., Vincent-Schneider, H., Briken, V., Yokozeki, T., Raposo, G., Bonnerot, C. (2002). Dynamics of Major Histocompatibility Complex Class II Compartments during B Cell Receptor-mediated Cell Activation. JEM 195: 461-472 [Abstract] [Full Text]
Nishioku, T., Hashimoto, K., Yamashita, K., Liou, S.-Y., Kagamiishi, Y., Maegawa, H., Katsube, N., Peters, C., von Figura, K., Saftig, P., Katunuma, N., Yamamoto, K., Nakanishi, H. (2002). Involvement of Cathepsin E in Exogenous Antigen Processing in Primary Cultured Murine Microglia. J. Biol. Chem. 277: 4816-4822 [Abstract] [Full Text]
Kleijmeer, M., Ramm, G., Schuurhuis, D., Griffith, J., Rescigno, M., Ricciardi-Castagnoli, P., Rudensky, A. Y., Ossendorp, F., Melief, C. J.M., Stoorvogel, W., Geuze, H. J. (2001). Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells. JCB 155: 53-64 [Abstract] [Full Text]
Shi, G.-P., Bryant, R. A.R., Riese, R., Verhelst, S., Driessen, C., Li, Z., Bromme, D., Ploegh, H. L., Chapman, H. A. (2000). Role for Cathepsin F in Invariant Chain Processing and Major Histocompatibility Complex Class II Peptide Loading by Macrophages. JEM 191: 1177-1186 [Abstract] [Full Text]