title: An orderly inactivation of intracellular retention signals controls surface expression of the T cell antigen receptor.
abstract: 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.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid 28049, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Balbino
authors.initials: B
authors.lastname: Alarcón
mesh_terms: 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
chemical_list: D017252:CD3 Complex; D017260:Receptor-CD3 Complex, Antigen, T-Cell
references.citation: EMBO J. 1995 May 15;14(10):2257-68
references.pmid: 7774584
references.citation: J Cell Biol. 1995 May;129(4):971-8
references.pmid: 7744968
references.citation: EMBO J. 1995 Oct 2;14(19):4641-53
references.pmid: 7588594
references.citation: J Biol Chem. 1996 May 10;271(19):11441-8
references.pmid: 8626701
references.citation: J Exp Med. 1996 Nov 1;184(5):1833-43
references.pmid: 8920871
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):616-21
references.pmid: 9012833
references.citation: Science. 1997 Jul 25;277(5325):556-8
references.pmid: 9228004
references.citation: J Cell Biol. 1997 Jul 28;138(2):271-81
references.pmid: 9230070
references.citation: Immunity. 1997 Jul;7(1):113-22
references.pmid: 9252124
references.citation: Immunity. 1997 Nov;7(5):591-9
references.pmid: 9390683
references.citation: Eur J Immunol. 1998 Jan;28(1):12-21
references.pmid: 9485181
references.citation: J Exp Med. 1998 Apr 6;187(7):1093-101
references.pmid: 9529325
references.citation: Science. 1998 May 8;280(5365):905-8
references.pmid: 9572735
references.citation: J Biol Chem. 1998 May 22;273(21):12807-16
references.pmid: 9582308
references.citation: J Biol Chem. 1998 Oct 9;273(41):26281-4
references.pmid: 9756853
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14909-14
references.pmid: 9843989
references.citation: J Exp Med. 2001 May 7;193(9):1045-58
references.pmid: 11342589
references.citation: Biochem Biophys Res Commun. 2002 Mar 8;291(4):751-7
references.pmid: 11866428
references.citation: Methods. 2002 Aug;27(4):311-7
references.pmid: 12217646
references.citation: J Immunol. 2002 Dec 1;169(11):6269-78
references.pmid: 12444133
references.citation: Proc Natl Acad Sci U S A. 1987 May;84(9):2688-92
references.pmid: 3495001
references.citation: J Biol Chem. 1988 Feb 25;263(6):2953-61
references.pmid: 2963821
references.citation: Cell. 1988 Jan 15;52(1):85-95
references.pmid: 3278811
references.citation: Eur J Immunol. 1989 May;19(5):947-50
references.pmid: 2472280
references.citation: EMBO J. 1989 Dec 1;8(12):3651-6
references.pmid: 2583115
references.citation: J Biol Chem. 1989 Dec 5;264(34):20760-9
references.pmid: 2531145
references.citation: Science. 1990 Jan 5;247(4938):79-82
references.pmid: 2294595
references.citation: Exp Mol Med. 1998 Sep 30;30(3):159-64
references.pmid: 9873838
references.citation: J Immunol. 1999 Jul 1;163(1):25-31
references.pmid: 10384095
references.citation: Eur J Immunol. 1990 Feb;20(2):299-305
references.pmid: 2138083
references.citation: Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1918-22
references.pmid: 2000396
references.citation: EMBO J. 1991 Apr;10(4):903-12
references.pmid: 1826255
references.citation: EMBO J. 1991 Jul;10(7):1643-51
references.pmid: 1828760
references.citation: Int Immunol. 1991 Apr;3(4):359-68
references.pmid: 1831654
references.citation: J Immunol. 1991 Nov 1;147(9):3047-52
references.pmid: 1717585
references.citation: Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10619-23
references.pmid: 1835791
references.citation: Curr Opin Cell Biol. 1991 Aug;3(4):592-600
references.pmid: 1772654
references.citation: Nature. 1992 Jun 18;357(6379):593-6
references.pmid: 1535117
references.citation: Cell. 1992 Jun 26;69(7):1143-57
references.pmid: 1535555
references.citation: Nature. 1992 Nov 19;360(6401):225-31
references.pmid: 1359428
references.citation: EMBO J. 1993 Nov;12(11):4347-55
references.pmid: 8223444
references.citation: EMBO J. 1993 Dec;12(12):4863-75
references.pmid: 8223495
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11401-5
references.pmid: 8248261
references.citation: Science. 1994 Jan 21;263(5145):387-90
references.pmid: 8278814
references.citation: EMBO J. 1994 Feb 15;13(4):784-97
references.pmid: 8112294
references.citation: Cell. 1994 Mar 11;76(5):853-64
references.pmid: 8124721
references.citation: Science. 1994 Mar 18;263(5153):1629-31
references.pmid: 8128252
references.citation: EMBO J. 1994 Apr 1;13(7):1696-705
references.pmid: 8157008
references.citation: EMBO J. 1994 May 1;13(9):2156-66
references.pmid: 8187769
references.citation: J Exp Med. 1994 Oct 1;180(4):1375-82
references.pmid: 7931071
references.citation: EMBO J. 1995 Jul 17;14(14):3425-33
references.pmid: 7628443