Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 5457K) PPT slides of all figures Supplemental Material Index 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 JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Takahashi, K. Articles by Miyake, K. Search for Related Content PubMed PubMed Citation Articles by Takahashi, K. Articles by Miyake, K. Social Bookmarking                            What's this?

¹ Division of Infectious Genetics and ² Division of Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan

CORRESPONDENCE Kensuke Miyake: kmiyake{at}ims.u-tokyo.ac.jp

Immune cells express multiple Toll-like receptors (TLRs) that are concomitantly activated by a variety of pathogen products. Although there is presumably a need to coordinate the expression and function of TLRs in individual cells, little is known about the mechanisms governing this process. We show that a protein associated with TLR4 (PRAT4A) is required for multiple TLR responses. PRAT4A resides in the endoplasmic reticulum, and PRAT4A knockdown inhibited trafficking of TLR1 and TLR4 to the cell surface and ligand-induced trafficking of TLR9 to lysosomes. Other cell-surface molecules were expressed normally on immunocytes from PRAT4A^–/– mice. There was impaired cytokine production to TLR ligands, except to the TLR3 ligand poly(I:C), and to whole bacteria. Activation of antigen-specific T helper type 1 responses were also defective. Moreover, PRAT4A^–/– bone marrow chimeric mice were resistant to lipopolysaccharide-induced sepsis. These results suggest that PRAT4A regulates the subcellular distribution and response of multiple TLRs and is required for both innate and adaptive immune responses.

K. Takahashi, T. Shibata, and S. Akashi-Takamura contributed equally to this study.

T. Kouro, Y. Nagai, and K. Takatsu's present address is Dept. of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama-shi, Toyama 930-0194, Japan.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Carpenter, S., Carlson, T., Dellacasagrande, J., Garcia, A., Gibbons, S., Hertzog, P., Lyons, A., Lin, L.-L., Lynch, M., Monie, T., Murphy, C., Seidl, K. J., Wells, C., Dunne, A., O'Neill, L. A. J. (2009). TRIL, a Functional Component of the TLR4 Signaling Complex, Highly Expressed in Brain. J. Immunol. 183: 3989-3995 [Abstract] [Full Text]  
• Nishitani, C., Takahashi, M., Mitsuzawa, H., Shimizu, T., Ariki, S., Matsushima, N., Kuroki, Y. (2009). Mutational analysis of Cys88 of Toll-like receptor 4 highlights the critical role of MD-2 in cell surface receptor expression. Int Immunol 21: 925-934 [Abstract] [Full Text]  
• Fukui, R., Saitoh, S.-i., Matsumoto, F., Kozuka-Hata, H., Oyama, M., Tabeta, K., Beutler, B., Miyake, K. (2009). Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing. JEM 206: 1339-1350 [Abstract] [Full Text]  
• Kiyokawa, T., Akashi-Takamura, S., Shibata, T., Matsumoto, F., Nishitani, C., Kuroki, Y., Seto, Y., Miyake, K. (2008). A single base mutation in the PRAT4A gene reveals differential interaction of PRAT4A with Toll-like receptors. Int Immunol 20: 1407-1415 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS