The Journal of Experimental Medicine
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 427K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yang, M.
Right arrow Articles by Weissman, A. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, M.
Right arrow Articles by Weissman, A. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/3/835/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 6, March 16, 1998 835-846

Articles

Novel Aspects of Degradation of T Cell Receptor Subunits from the Endoplasmic Reticulum (ER) in T Cells: Importance of Oligosaccharide Processing, Ubiquitination, and Proteasome-dependent Removal from ER Membranes

Mei Yang*, Satoshi Omura{ddagger}, Juan S. Bonifacino§, and Allan M. Weissman*

From the * Laboratory of Immune Cell Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1152; {ddagger} The Kitasato Institute, Tokyo, Japan; and the § Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430

Expression of the T cell antigen receptor (TCR) on the surface of thymocytes and mature T cells is dependent on the assembly of receptor subunits into TCRs in the endoplasmic reticulum (ER) and their successful traversal of the secretory pathway to the plasma membrane. TCR subunits that fail to exit the ER for the Golgi complex are degraded by nonlysosomal processes that have been referred to as "ER degradation". The molecular basis for the loss of the TCR CD3-{delta} and TCR-{alpha} subunits from the ER was investigated in lymphocytes. For CD3-{delta}, we describe a process leading to its degradation that includes trimming of mannose residues from asparagine-linked (N-linked) oligosaccharides, generation of ubiquitinated membrane-bound intermediates, and proteasome-dependent removal from the ER membrane. When either mannosidase activity or the catalytic activity of proteasomes was inhibited, loss of CD3-{delta} was markedly curtailed and CD3-{delta} remained membrane bound in a complex with CD3-{varepsilon}. TCR-{alpha} was also found to be degraded in a proteasome-dependent manner with ubiquitinated intermediates. However, no evidence of a role for mannosidases was found for TCR-{alpha}, and significant retrograde movement through the ER membrane took place even when proteasome function was inhibited. These findings provide new insights into mechanisms employed to regulate levels of TCRs, and underscore that cells use multiple mechanisms to target proteins from the ER to the cytosol for degradation.

Address correspondence to Allan M. Weissman, Bldg. 10, Rm. 1B34, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1152. Phone: 301-496-3557; Fax: 301-402-4844; E-mail: amw{at}nih.gov

1Abbreviations used in this paper: anti-Ub, anti-ubiquitin; CA, control antiserum; CFTR, cystic fibrosis conductance regulator; CHX, cycloheximide; dMNJ, deoxymannojirimycin; dMJ, deoxynojirimycin; ER, endoplasmic reticulum; Glc, glucose; GlcNAc, N-acetyl glucosamine; LCN, lactacystin; LLM, LLnL, N-acetyl-Leu-Leu-methioninal; N-acetyl-Leu-Leu-norleucinal; Man, mannose; Mg132, Z-Leu-Leu-Leu CHO.


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS