title: Exit of the pre-TCR from the ER/cis-Golgi is necessary for signaling differentiation, proliferation, and allelic exclusion in immature thymocytes.
abstract: A major issue is whether surface expression of the pre-TCR is necessary for signaling the development of immature thymocytes. To address this question, we generated transgenic mice expressing a TCRbeta chain that had a strong endoplasmic reticulum (ER) retrieval signal (TCRbetaER) and that was expressed intracellularly but failed to reach the cell surface. In TCRbetaER transgenic mice, there was a failure of allelic exclusion. Also, the transgene failed to rescue the developmental defects observed in TCRbeta-null mice. In contrast, TCRbeta transgenes with a mutant ER retrieval sequence or lacking this sequence signaled efficient allelic exclusion and suppressed the TCRbeta-/- defect. These data show that exit of the pre-TCR from the ER/cis-Golgi is required for progression through the double-negative thymocyte checkpoint.
authors.affiliation: Imperial Cancer Research Fund, Lincoln's Inn Fields, London, United Kingdom.
authors.forename: C C
authors.initials: CC
authors.lastname: O'Shea
authors.forename: A P
authors.initials: AP
authors.lastname: Thornell
authors.forename: I R
authors.initials: IR
authors.lastname: Rosewell
authors.forename: B
authors.initials: B
authors.lastname: Hayes
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D002118:Calcium