An endoplasmic reticulum retention function for the cytoplasmic tail of the human pre-T cell receptor (TCR) α chain:: Potential role in the regulation of cell surface pre-TCR expression levels
An endoplasmic reticulum retention function for the cytoplasmic tail of the human pre-T cell receptor (TCR) α chain:: Potential role in the regulation of cell surface pre-TCR expression levels
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DOI：
10.1084/jem.193.9.1045
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发表时间：
2001-05-07
影响因子：
15.3
通讯作者：
Toribio, ML
中科院分区：
文献类型：
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作者：
Carrasco, YR;Ramiro, AR;Toribio, ML
前T细胞受体（TCR）由与前TCR-α（pT α）配对并与CD 3/zeta组分相关的TCR-β链组成，是T细胞发育的关键调节因子。由于未知的原因，极低的前TCR水平到达前T细胞的质膜。通过将嵌合TCR-α-pT α蛋白转染到前T和成熟T细胞系中，我们在此表明人前TCR的低表面表达是pT α链依赖性的。特别地，ρ Τ α的胞质结构域足以将常规TCR-α/β的表面表达降低至前TCR表达水平。这种降低的表达不能归因于与前TCR和TCR表面复合物相关的CD 3/zeta模块的生物化学组成的定性差异。相反，提供了证据表明pT α胞质尾区也导致单个膜分子如CD 25和CD 4的表面表达降低，这些膜分子显示保留在内质网（ER）中。还观察到天然pT α主要定位于ER。最后，沿着pT α胞质结构域的连续截短揭示了去除COOH-末端48个残基足以从ER滞留中释放CD-4-pT α嵌合体，并恢复天然CD 4表面表达水平。因此，pT α的截短也与增强的前TCR表达相关。观察到的pT α ER保留功能可能有助于调节前T细胞上的表面前TCR表达。
The pre-T cell receptor (TCR), which consists of a TCR-beta chain paired with pre-TCR-alpha (pT alpha) and associated with CD3/zeta components, is a critical regulator of T cell development. For unknown reasons, extremely low pre-TCR levels reach the plasma membrane of pre-T cells, By transfecting chimeric TCR-alpha -pT alpha proteins into pre-T and mature T cell lines, we show here that the low surface expression of the human pre-TCR is pT alpha chain dependent. Particularly, the cytoplasmic domain of pT alpha is sufficient to reduce surface expression of a conventional TCR-alpha/beta to pre-TCR expression levels. Such reduced expression cannot be attributed to qualitative differences in the biochemical composition of the CD3/zeta modules associated with pre-TCR and TCR surface complexes, Rather, evidence is provided that the pT alpha cytoplasmic tail also causes a reduced surface expression of individual membrane molecules such as CD25 and CD4, which are shown to be retained in the endoplasmic reticulum (ER). Native pT alpha is also observed to be predominantly ER localized. Finally, sequential truncations along the pT alpha cytoplasmic domain revealed that removal of the COOH-terminal 48 residues is sufficient to release a CD-4-pT alpha chimera from ER retention, and to restore native CD4 surface expression levels. As such a truncation in pT alpha also correlates with enhanced pre-TCR expression. the observed pT alpha ER retention function may contribute to the regulation of surface pre-TCR expression on pre-T cells.