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An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor

AuthorsDelgado, Pilar ; Alarcón, Balbino
KeywordsT cell receptor
Issue Date21-Feb-2005
PublisherRockefeller University Press
CitationJournal of Experimental Medicine Vol. 201, No. 4, 2005, 555–566
AbstractExit from the endoplasmic reticulum (ER) is an important checkpoint for proper assembly of multimeric plasma membrane receptors. The six subunits of the T cell receptor (TCR; TCR, TCRß, CD3, CD3, CD3, and CD3) are each endowed with ER retention/retrieval signals, and regulation of its targeting to the plasma membrane is therefore especially intriguing. We have studied the importance of the distinct ER retention signals at different stages of TCR intracellular assembly. To this end, we have characterized first the presence of ER retention signals in CD3. Despite the presence of multiple ER retention signals in CD3, dimers reach the cell surface when the single CD3 ER retention signal is deleted. Furthermore, inclusion of this CD3 mutant promoted plasma membrane expression of incomplete ß and ß complexes without CD3. It therefore appears that the CD3 ER retention signal is dominant and that it is only overridden upon the incorporation of CD3. We propose that the stepwise assembly of the TCR complex guarantees that all assembly intermediates have at least one functional ER retention signal and that only a full signaling-competent TCR complex is expressed on the cell surface
Description12 pages.-- Supplementary material available at: http://www.jem.org/cgi/content/full/jem.20041133/DC1
Publisher version (URL)http://dx.doi.org/10.1084/jem.20041133
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