

Lauritsen, Jens Peter H Bonefeld, Charlotte Menné von Essen, MarinaĬontaining the di-leucine-based endocytosis motif of the TCR subunit CD3 gamma have indicated that the zeta chain can mask this motif. Masking of the CD3 gamma di-leucine-based motif by zeta is required for efficient T-cell receptor expression Based on the present results and previously published observations on intracellular receptor sorting, a general model for intracellular sorting of receptors containing di-leucine- or tyrosine-based motifs is proposed. Point mutation analyses confirmed this observation and demonstrated that a membrane-proximal di-leucine motif (L131., indicating that the TCR was down-regulated by endocytosis via clathrin coated pits.
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Furthermore, analysis of a series of CD3 gamma truncation mutants indicated that in addition to S126 phosphorylation a motif C-terminal of S126 was required for TCR down-regulation. Mutations in the di-arginine motif of the Sigma 1-type opioid receptor, the beta-subunit of the signal recognition particle receptor, and Sterol-O-acyltransferase, three proteins identified in our bioinformatic screen also caused mislocalization of these known ER-resident proteins.We conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.ĬD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor Bioinformatic analysis determined that the di-arginine motif is present in the first 25 residues in a large number of all ER/SR Gene Ontology (GO annotated proteins. Our data show that PLN is recycled via the retrograde Golgi to ER membrane traffic pathway involving COP-I vesicles, since co-immunoprecipitation assays determined that COP I interactions are dependent on an intact di-arginine motif as PLN RDelta14 did not co-precipitate with COP I containing vesicles. Here we were interested in determining the cellular mechanisms involved in this disease-causing mutation.Mutations deleting codons for either or both Arg13 or Arg14 resulted in the mislocalization of PLN from the ER.

A mutation of PLN in which one of the di-arginine residues at positions 13 and 14 was deleted led to a severe, early onset dilated cardiomyopathy. In this study, we show that protein kinase C-induced TCR down.Įndoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?ĭirectory of Open Access Journals (Sweden)įull Text Available Phospholamban (PLN is an effective inhibitor of the sarco(endoplasmic reticulum Ca(2+-ATPase, which transports Ca(2+ into the SR lumen, leading to muscle relaxation. However, the role of the CD3γ diL motif in T-cell development is not known. In this study, we show that protein kinase C-induced TCR down-regulatio.The CD3γ di-leucine-based ( diL) receptor-sorting motif plays a central role in TCR down-regulation and in clonal expansion of virus-specific T cells. The CD3γ di-leucine-based ( diL) receptor-sorting motif plays a central role in TCR down-regulation and in clonal expansion of virus-specific T cells. Lauritsen, Jens Peter Holst Boding, Lasse Buus, Terkild B

Fine-tuning of T-cell development by the CD3γ di-leucine-based TCR-sorting motif
