Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 307 (5709): 593-596

Copyright © 2005 by the American Association for the Advancement of Science

Endogenous MHC Class II Processing of a Viral Nuclear Antigen After Autophagy

Casper Paludan,1,2* Dorothee Schmid,1,2* Markus Landthaler,3 Martina Vockerodt,4 Dieter Kube,5 Thomas Tuschl,3 Christian Münz1,2{dagger}

Abstract: CD4+ T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acidification, EBNA1, the dominant CD4+ T cell antigen of latent Epstein-Barr virus infection, slowly accumulated in cytosolic autophagosomes. In addition, inhibition of autophagy decreased recognition by EBNA1-specific CD4+ T cell clones. Thus, lysosomal processing after autophagy may contribute to MHC class II–restricted surveillance of long-lived endogenous antigens including nuclear proteins relevant to disease.

1 Laboratory of Viral Immunobiology, Rockefeller University, New York, NY 10021, USA.
2 Christopher H. Browne Center for Immunology and Immune Diseases, Rockefeller University, New York, NY 10021, USA.
3 Laboratory of RNA Molecular Biology, Rockefeller University, New York, NY 10021, USA.
4 Pediatrics I, Georg August University of Göttingen, 37099 Göttingen, Germany.
5 Center for Internal Medicine, Hematology, and Oncology, Georg August University of Göttingen, 37099 Göttingen, Germany.

Back to Top

* These authors contributed equally to the presented work.

{dagger} To whom correspondence should be addressed. E-mail: munzc{at}mail.rockefeller.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
MHC II tetramers visualize human CD4+ T cell responses to Epstein-Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response.
H. M. Long, O. L. Chagoury, A. M. Leese, G. B. Ryan, E. James, L. T. Morton, R. J. M. Abbott, S. Sabbah, W. Kwok, and A. B. Rickinson (2013)
J. Exp. Med. 210, 933-949
   Abstract »    Full Text »    PDF »
CaMKI{alpha} Regulates AMP Kinase-Dependent, TORC-1-Independent Autophagy during Lipopolysaccharide-Induced Acute Lung Neutrophilic Inflammation.
L. Guo, J. L. Stripay, X. Zhang, R. D. Collage, M. Hulver, E. H. Carchman, G. M. Howell, B. S. Zuckerbraun, J. S. Lee, and M. R. Rosengart (2013)
J. Immunol. 190, 3620-3628
   Abstract »    Full Text »    PDF »
Macroautophagy substrates are loaded onto MHC class II of medullary thymic epithelial cells for central tolerance.
M. Aichinger, C. Wu, J. Nedjic, and L. Klein (2013)
J. Exp. Med. 210, 287-300
   Abstract »    Full Text »    PDF »
Active Escape of Orientia tsutsugamushi from Cellular Autophagy.
Y. Ko, J.-H. Choi, N.-Y. Ha, I.-S. Kim, N.-H. Cho, and M.-S. Choi (2013)
Infect. Immun. 81, 552-559
   Abstract »    Full Text »    PDF »
Autophagy and selective deployment of Atg proteins in antiviral defense.
B. Yordy, M. C. Tal, K. Hayashi, O. Arojo, and A. Iwasaki (2013)
Int. Immunol. 25, 1-10
   Abstract »    Full Text »    PDF »
Replication of Epstein-Barr Viral DNA.
W. Hammerschmidt and B. Sugden (2013)
Cold Spring Harb Perspect Biol 5, a013029
   Abstract »    Full Text »    PDF »
Regulatory T cells that recognize a ubiquitous stress-inducible self-antigen are long-lived suppressors of autoimmune arthritis.
M. J. C. van Herwijnen, L. Wieten, R. van der Zee, P. J. van Kooten, J. P. Wagenaar-Hilbers, A. Hoek, I. den Braber, S. M. Anderton, M. Singh, H. D. Meiring, et al. (2012)
PNAS 109, 14134-14139
   Abstract »    Full Text »    PDF »
Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway.
S.-K. Tey and R. Khanna (2012)
Blood 120, 994-1004
   Abstract »    Full Text »    PDF »
Autophagy: An Emerging Immunological Paradigm.
V. Deretic (2012)
J. Immunol. 189, 15-20
   Abstract »    Full Text »    PDF »
Immortalized clones of fibroblastic reticular cells activate virus-specific T cells during virus infection.
C. T. Ng, B. P. Nayak, C. Schmedt, and M. B. A. Oldstone (2012)
PNAS 109, 7823-7828
   Abstract »    Full Text »    PDF »
Drosophila Golgi membrane protein Ema promotes autophagosomal growth and function.
S. Kim, S. A. Naylor, and A. DiAntonio (2012)
PNAS 109, E1072-E1081
   Abstract »    Full Text »    PDF »
Heat Shock Protein 90-Mediated Peptide-Selective Presentation of Cytosolic Tumor Antigen for Direct Recognition of Tumors by CD4+ T Cells.
T. Tsuji, J. Matsuzaki, O. L. Caballero, A. A. Jungbluth, G. Ritter, K. Odunsi, L. J. Old, and S. Gnjatic (2012)
J. Immunol. 188, 3851-3858
   Abstract »    Full Text »    PDF »
The Human Cytomegalovirus Protein TRS1 Inhibits Autophagy via Its Interaction with Beclin 1.
M. Chaumorcel, M. Lussignol, L. Mouna, Y. Cavignac, K. Fahie, J. Cotte-Laffitte, A. Geballe, W. Brune, I. Beau, P. Codogno, et al. (2012)
J. Virol. 86, 2571-2584
   Abstract »    Full Text »    PDF »
T-cell immunity to Kaposi sarcoma-associated herpesvirus: recognition of primary effusion lymphoma by LANA-specific CD4+ T cells.
S. Sabbah, Y. J. Jagne, J. Zuo, T. de Silva, M. M. Ahasan, C. Brander, S. Rowland-Jones, K. L. Flanagan, and A. D. Hislop (2012)
Blood 119, 2083-2092
   Abstract »    Full Text »    PDF »
Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells.
J. M. Ireland and E. R. Unanue (2011)
J. Exp. Med. 208, 2625-2632
   Abstract »    Full Text »    PDF »
Innate Immune Activation and Thyroid Autoimmunity.
A. Kawashima, K. Tanigawa, T. Akama, A. Yoshihara, N. Ishii, and K. Suzuki (2011)
J. Clin. Endocrinol. Metab. 96, 3661-3671
   Abstract »    Full Text »    PDF »
IKK{beta} and NF-{kappa}B Transcription Govern Lymphoma Cell Survival through AKT-Induced Plasma Membrane Trafficking of GLUT1.
T. G. Sommermann, K. O'Neill, D. R. Plas, and E. Cahir-McFarland (2011)
Cancer Res. 71, 7291-7300
   Abstract »    Full Text »    PDF »
Activation of Autophagy by {alpha}-Herpesviruses in Myeloid Cells Is Mediated by Cytoplasmic Viral DNA through a Mechanism Dependent on Stimulator of IFN Genes.
S. B. Rasmussen, K. A. Horan, C. K. Holm, A. J. Stranks, T. C. Mettenleiter, A. K. Simon, S. B. Jensen, F. J. Rixon, B. He, and S. R. Paludan (2011)
J. Immunol. 187, 5268-5276
   Abstract »    Full Text »    PDF »
A Cytosolic Phospholipase A2-Initiated Lipid Mediator Pathway Induces Autophagy in Macrophages.
H.-Y. Qi, M. P. Daniels, Y. Liu, L.-Y. Chen, S. Alsaaty, S. J. Levine, and J. H. Shelhamer (2011)
J. Immunol. 187, 5286-5292
   Abstract »    Full Text »    PDF »
Autophagy-Mediated Dendritic Cell Activation Is Essential for Innate Cytokine Production and APC Function with Respiratory Syncytial Virus Responses.
S. Morris, M. S. Swanson, A. Lieberman, M. Reed, Z. Yue, D. M. Lindell, and N. W. Lukacs (2011)
J. Immunol. 187, 3953-3961
   Abstract »    Full Text »    PDF »
Crohn's disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2.
T. S. Plantinga, T. O. Crisan, M. Oosting, F. L. van de Veerdonk, D. J. de Jong, D. J. Philpott, J. W. M. van der Meer, S. E. Girardin, L. A. B. Joosten, and M. G. Netea (2011)
Gut 60, 1229-1235
   Abstract »    Full Text »    PDF »
Functional Macroautophagy Induction by Influenza A Virus without a Contribution to Major Histocompatibility Complex Class II-Restricted Presentation.
J. D. Comber, T. M. Robinson, N. A. Siciliano, A. E. Snook, and L. C. Eisenlohr (2011)
J. Virol. 85, 6453-6463
   Abstract »    Full Text »    PDF »
The multiple roles of autophagy in cancer.
M. T. Rosenfeldt and K. M. Ryan (2011)
Carcinogenesis 32, 955-963
   Abstract »    Full Text »    PDF »
Cytotoxic CD4+ T Cell Responses to EBV Contrast with CD8 Responses in Breadth of Lytic Cycle Antigen Choice and in Lytic Cycle Recognition.
H. M. Long, A. M. Leese, O. L. Chagoury, S. R. Connerty, J. Quarcoopome, L. L. Quinn, C. Shannon-Lowe, and A. B. Rickinson (2011)
J. Immunol. 187, 92-101
   Abstract »    Full Text »    PDF »
Dynamics of the Degradation of Ubiquitinated Proteins by Proteasomes and Autophagy: ASSOCIATION WITH SEQUESTOSOME 1/p62.
N. Myeku and M. E. Figueiredo-Pereira (2011)
J. Biol. Chem. 286, 22426-22440
   Abstract »    Full Text »    PDF »
Proteasomes, TAP, and Endoplasmic Reticulum-Associated Aminopeptidase Associated with Antigen Processing Control CD4+ Th Cell Responses by Regulating Indirect Presentation of MHC Class II-Restricted Cytoplasmic Antigens.
S. M. Dragovic, T. Hill, G. J. Christianson, S. Kim, T. Elliott, D. Scott, D. C. Roopenian, L. Van Kaer, and S. Joyce (2011)
J. Immunol. 186, 6683-6692
   Abstract »    Full Text »    PDF »
Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 3 Inhibits Gamma Interferon and Major Histocompatibility Complex Class II Expression.
K. Schmidt, E. Wies, and F. Neipel (2011)
J. Virol. 85, 4530-4537
   Abstract »    Full Text »    PDF »
Temporal Regulation of Intracellular Organelle Homeostasis in T Lymphocytes by Autophagy.
W. Jia and Y.-W. He (2011)
J. Immunol. 186, 5313-5322
   Abstract »    Full Text »    PDF »
Autophagy Controls IL-1{beta} Secretion by Targeting Pro-IL-1{beta} for Degradation.
J. Harris, M. Hartman, C. Roche, S. G. Zeng, A. O'Shea, F. A. Sharp, E. M. Lambe, E. M. Creagh, D. T. Golenbock, J. Tschopp, et al. (2011)
J. Biol. Chem. 286, 9587-9597
   Abstract »    Full Text »    PDF »
Alternative Endogenous Protein Processing via an Autophagy-Dependent Pathway Compensates for Yersinia-Mediated Inhibition of Endosomal Major Histocompatibility Complex Class II Antigen Presentation.
H. Russmann, K. Panthel, B. Kohn, S. Jellbauer, S. E. Winter, S. Garbom, H. Wolf-Watz, S. Hoffmann, S. Grauling-Halama, and G. Geginat (2010)
Infect. Immun. 78, 5138-5150
   Abstract »    Full Text »    PDF »
Coxsackievirus Infection Induces Autophagy-Like Vesicles and Megaphagosomes in Pancreatic Acinar Cells In Vivo.
C. C. Kemball, M. Alirezaei, C. T. Flynn, M. R. Wood, S. Harkins, W. B. Kiosses, and J. L. Whitton (2010)
J. Virol. 84, 12110-12124
   Abstract »    Full Text »    PDF »
Regulation of Mammalian Autophagy in Physiology and Pathophysiology.
B. Ravikumar, S. Sarkar, J. E. Davies, M. Futter, M. Garcia-Arencibia, Z. W. Green-Thompson, M. Jimenez-Sanchez, V. I. Korolchuk, M. Lichtenberg, S. Luo, et al. (2010)
Physiol Rev 90, 1383-1435
   Abstract »    Full Text »    PDF »
Expansion of EBNA1-specific effector T cells in posttransplantation lymphoproliferative disorders.
K. Jones, J. P. Nourse, L. Morrison, D. Nguyen-Van, D. J. Moss, S. R. Burrows, and M. K. Gandhi (2010)
Blood 116, 2245-2252
   Abstract »    Full Text »    PDF »
TLR9 Contributes to the Recognition of EBV by Primary Monocytes and Plasmacytoid Dendritic Cells.
S. Fiola, D. Gosselin, K. Takada, and J. Gosselin (2010)
J. Immunol. 185, 3620-3631
   Abstract »    Full Text »    PDF »
Regulation of innate immune responses by autophagy-related proteins.
T. Saitoh and S. Akira (2010)
J. Cell Biol. 189, 925-935
   Abstract »    Full Text »    PDF »
Immune evasion by gammaherpesvirus genome maintenance proteins.
N. Blake (2010)
J. Gen. Virol. 91, 829-846
   Abstract »    Full Text »    PDF »
Autophagy in health and disease. 1. Regulation and significance of autophagy: an overview.
M. Mehrpour, A. Esclatine, I. Beau, and P. Codogno (2010)
Am J Physiol Cell Physiol 298, C776-C785
   Abstract »    Full Text »    PDF »
Hsp90 inhibitors block outgrowth of EBV-infected malignant cells in vitro and in vivo through an EBNA1-dependent mechanism.
X. Sun, E. A. Barlow, S. Ma, S. R. Hagemeier, S. J. Duellman, R. R. Burgess, J. Tellam, R. Khanna, and S. C. Kenney (2010)
PNAS 107, 3146-3151
   Abstract »    Full Text »    PDF »
Nuclear location of an endogenously expressed antigen, EBNA1, restricts access to macroautophagy and the range of CD4 epitope display.
C. S. Leung, T. A. Haigh, L. K. Mackay, A. B. Rickinson, and G. S. Taylor (2010)
PNAS 107, 2165-2170
   Abstract »    Full Text »    PDF »
Interaction of ICP34.5 with Beclin 1 Modulates Herpes Simplex Virus Type 1 Pathogenesis through Control of CD4+ T-Cell Responses.
D. A. Leib, D. E. Alexander, D. Cox, J. Yin, and T. A. Ferguson (2009)
J. Virol. 83, 12164-12171
   Abstract »    Full Text »    PDF »
Autophagic Compartments Gain Access to the MHC Class II Compartments in Thymic Epithelium.
M. Kasai, I. Tanida, T. Ueno, E. Kominami, S. Seki, T. Ikeda, and T. Mizuochi (2009)
J. Immunol. 183, 7278-7285
   Abstract »    Full Text »    PDF »
Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection.
J. B. Sacha, J. P. Giraldo-Vela, M. B. Buechler, M. A. Martins, N. J. Maness, C. Chung, L. T. Wallace, E. J. Leon, T. C. Friedrich, N. A. Wilson, et al. (2009)
PNAS 106, 9791-9796
   Abstract »    Full Text »    PDF »
Activation of antibacterial autophagy by NADPH oxidases.
J. Huang, V. Canadien, G. Y. Lam, B. E. Steinberg, M. C. Dinauer, M. A. O. Magalhaes, M. Glogauer, S. Grinstein, and J. H. Brumell (2009)
PNAS 106, 6226-6231
   Abstract »    Full Text »    PDF »
Autophagy Is Essential for Mitochondrial Clearance in Mature T Lymphocytes.
H. H. Pua, J. Guo, M. Komatsu, and Y.-W. He (2009)
J. Immunol. 182, 4046-4055
   Abstract »    Full Text »    PDF »
Autophagy and Its Role in MHC-Mediated Antigen Presentation.
V. L. Crotzer and J. S. Blum (2009)
J. Immunol. 182, 3335-3341
   Abstract »    Full Text »    PDF »
Down-Regulation of MHC Class II Expression through Inhibition of CIITA Transcription by Lytic Transactivator Zta during Epstein-Barr Virus Reactivation.
D. Li, L. Qian, C. Chen, M. Shi, M. Yu, M. Hu, L. Song, B. Shen, and N. Guo (2009)
J. Immunol. 182, 1799-1809
   Abstract »    Full Text »    PDF »
Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation.
K. Li, K. J. Anderson, Q. Peng, A. Noble, B. Lu, A. P. Kelly, N. Wang, S. H. Sacks, and W. Zhou (2008)
Blood 112, 5084-5094
   Abstract »    Full Text »    PDF »
Efficient Cross-presentation Depends on Autophagy in Tumor Cells.
Y. Li, L.-X. Wang, G. Yang, F. Hao, W. J. Urba, and H.-M. Hu (2008)
Cancer Res. 68, 6889-6895
   Abstract »    Full Text »    PDF »
Apolipoprotein L1, a Novel Bcl-2 Homology Domain 3-only Lipid-binding Protein, Induces Autophagic Cell Death.
G. Wan, S. Zhaorigetu, Z. Liu, R. Kaini, Z. Jiang, and C.-a. A. Hu (2008)
J. Biol. Chem. 283, 21540-21549
   Abstract »    Full Text »    PDF »
B Cells Induce Tolerance by Presenting Endogenous Peptide-IgG on MHC Class II Molecules via an IFN-{gamma}-Inducible Lysosomal Thiol Reductase-Dependent Pathway.
Y. Su, G. Carey, M. Maric, and D. W. Scott (2008)
J. Immunol. 181, 1153-1160
   Abstract »    Full Text »    PDF »
Hepatitis C Virus Genotype 1a Growth and Induction of Autophagy.
M. Ait-Goughoulte, T. Kanda, K. Meyer, J. S. Ryerse, R. B. Ray, and R. Ray (2008)
J. Virol. 82, 2241-2249
   Abstract »    Full Text »    PDF »
CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals.
L. Crompton, N. Khan, R. Khanna, L. Nayak, and P. A. H. Moss (2008)
Blood 111, 2053-2061
   Abstract »    Full Text »    PDF »
Gtdap-1 promotes autophagy and is required for planarian remodeling during regeneration and starvation.
C. Gonzalez-Estevez, D. A. Felix, A. A. Aboobaker, and E. Salo (2007)
PNAS 104, 13373-13378
   Abstract »    Full Text »    PDF »
Epstein-Barr Virus: Environmental Trigger of Multiple Sclerosis?.
J. D. Lunemann, T. Kamradt, R. Martin, and C. Munz (2007)
J. Virol. 81, 6777-6784
   Full Text »    PDF »
Herpesvirus Interference with Major Histocompatibility Complex Class II-Restricted T-Cell Activation.
E. J. Wiertz, R. Devlin, H. L. Collins, and M. E. Ressing (2007)
J. Virol. 81, 4389-4396
   Full Text »    PDF »
Adenovirus-Specific CD4+ T Cell Clones Recognizing Endogenous Antigen Inhibit Viral Replication In Vitro through Cognate Interaction.
B. Heemskerk, T. van Vreeswijk, L. A. Veltrop-Duits, C. C. Sombroek, K. Franken, R. M. Verhoosel, P. S. Hiemstra, D. van Leeuwen, M. E. Ressing, R. E. M. Toes, et al. (2006)
J. Immunol. 177, 8851-8859
   Abstract »    Full Text »    PDF »
Autophagy: Eating for Good Health.
M. S. Swanson (2006)
J. Immunol. 177, 4945-4951
   Abstract »    Full Text »    PDF »
A Role for Intercellular Antigen Transfer in the Recognition of EBV-Transformed B Cell Lines by EBV Nuclear Antigen-Specific CD4+ T Cells.
G. S. Taylor, H. M. Long, T. A. Haigh, M. Larsen, J. Brooks, and A. B. Rickinson (2006)
J. Immunol. 177, 3746-3756
   Abstract »    Full Text »    PDF »
Human IRGM Induces Autophagy to Eliminate Intracellular Mycobacteria.
S. B. Singh, A. S. Davis, G. A. Taylor, and V. Deretic (2006)
Science 313, 1438-1441
   Abstract »    Full Text »    PDF »
Autophagy in Innate Immunity against Intracellular Bacteria.
A. Amano, I. Nakagawa, and T. Yoshimori (2006)
J. Biochem. 140, 161-166
   Abstract »    Full Text »    PDF »
Macrophage cultures are susceptible to lytic productive infection by endothelial-cell-propagated human cytomegalovirus strains and present viral IE1 protein to CD4+ T cells despite late downregulation of MHC class II molecules.
C. Sinzger, K. Eberhardt, Y. Cavignac, C. Weinstock, T. Kessler, G. Jahn, and J.-L. Davignon (2006)
J. Gen. Virol. 87, 1853-1862
   Abstract »    Full Text »    PDF »
Association of Antigen-Processing Machinery and HLA Antigen Phenotype of Melanoma Cells with Survival in American Joint Committee on Cancer Stage III and IV Melanoma Patients..
A. Anichini, R. Mortarini, D. Nonaka, A. Molla, C. Vegetti, E. Montaldi, X. Wang, and S. Ferrone (2006)
Cancer Res. 66, 6405-6411
   Abstract »    Full Text »    PDF »
Virus-specific CD4+ T cells: ready for direct attack.
K. N. Heller, C. Gurer, and C. Munz (2006)
J. Exp. Med. 203, 805-808
   Abstract »    Full Text »    PDF »
Autophagic programmed cell death by selective catalase degradation.
L. Yu, F. Wan, S. Dutta, S. Welsh, Z. Liu, E. Freundt, E. H. Baehrecke, and M. Lenardo (2006)
PNAS 103, 4952-4957
   Abstract »    Full Text »    PDF »
Molecular Mechanisms and Regulation of Specific and Nonspecific Autophagy Pathways in Yeast.
U. Nair and D. J. Klionsky (2005)
J. Biol. Chem. 280, 41785-41788
   Full Text »    PDF »
Long-Term MHC Class II Presentation of the EBV Lytic Protein BHRF1 by EBV Latently Infected B Cells following Capture of BHRF1 Antigen.
E. Landais, X. Saulquin, M. Bonneville, and E. Houssaint (2005)
J. Immunol. 175, 7939-7946
   Abstract »    Full Text »    PDF »
Optimization of CD4+ T Lymphocyte Response to Human Cytomegalovirus Nuclear IE1 Protein through Modifications of Both Size and Cellular Localization.
S. Delmas, L. Martin, M. Baron, J. A. Nelson, D. N. Streblow, and J.-L. Davignon (2005)
J. Immunol. 175, 6812-6819
   Abstract »    Full Text »    PDF »
Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes.
G. Barba-Spaeth, R. S. Longman, M. L. Albert, and C. M. Rice (2005)
J. Exp. Med. 202, 1179-1184
   Abstract »    Full Text »    PDF »
Autophagy and intracellular surveillance: Modulating MHC class II antigen presentation with stress.
V. L. Crotzer and J. S. Blum (2005)
PNAS 102, 7779-7780
   Full Text »    PDF »
Autophagy promotes MHC class II presentation of peptides from intracellular source proteins.
J. Dengjel, O. Schoor, R. Fischer, M. Reich, M. Kraus, M. Muller, K. Kreymborg, F. Altenberend, J. Brandenburg, H. Kalbacher, et al. (2005)
PNAS 102, 7922-7927
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882