An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor.
Exit 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; TCRalpha, TCRbeta, CD3gamma, CD3delta, CD3epsilon, and CD3zeta) 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 CD3gamma. Despite the presence of multiple ER retention signals in CD3gamma, epsilongamma dimers reach the cell surface when the single CD3epsilon ER retention signal is deleted. Furthermore, inclusion of this CD3epsilon mutant promoted plasma membrane expression of incomplete alphabetagammaepsilon and alphabetadeltaepsilon complexes without CD3zeta. It therefore appears that the CD3epsilon ER retention signal is dominant and that it is only overridden upon the incorporation of CD3zeta. 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.
Delgado
Pilar
P
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid 28049, Spain.
Alarcón
Balbino
B
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D051379:Mice; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction
D017252:CD3 Complex; D017260:Receptor-CD3 Complex, Antigen, T-Cell
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