NEF INDUCES CD4 ENDOCYTOSIS - REQUIREMENT FOR A CRITICAL DILEUCINE MOTIF IN THE MEMBRANE-PROXIMAL CD4 CYTOPLASMIC DOMAIN
NEF INDUCES CD4 ENDOCYTOSIS - REQUIREMENT FOR A CRITICAL DILEUCINE MOTIF IN THE MEMBRANE-PROXIMAL CD4 CYTOPLASMIC DOMAIN
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DOI：
10.1016/0092-8674(94)90360-3
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发表时间：
1994-03-11
期刊：
影响因子：
64.5
通讯作者：
TRONO, D
中科院分区：
文献类型：
--
作者：
AIKEN, C;KONNER, J;TRONO, D
CD4对于抗原驱动的辅助性T细胞信号传导至关重要，并被人类免疫缺陷病毒（HIV）用作受体。HIV早期蛋白Nef通过先前未定义的转录后机制导致细胞表面CD4的损失。在这里，我们证明Nef通过诱导CD4内吞作用发挥作用，导致其在溶酶体中降解。Nef通过豆蔻酰化与细胞膜的结合强烈增强了CD4的下调。嵌合分子的研究表明，CD4胞质结构域的20个膜近端残基足以赋予Nef敏感性。在该区域内，双亮氨酸基序，使人想起在CD3 γ和δ链中发现的内吞作用和溶酶体靶向信号，对于CD4对Nef的应答至关重要。
CD4 is crucial for antigen-driven helper T cell signaling and is used as receptor by the human immunodeficiency virus (HIV). The HIV early protein Nef causes a loss of CD4 from cell surfaces through a previously undefined posttranscriptional mechanism. Here, we demonstrate that Nef acts by inducing CD4 endocytosis, resulting in its degradation in lysosomes. CD4 down-regulation is strongly enhanced by the association of Nef with cell membranes through myristoylation. The study of chimeric molecules reveals that 20 membrane-proximal residues of the CD4 cytoplasmic domain are sufficient to confer Nef sensitivity. Within this region, a dileucine motif, reminiscent of an endocytosis and lysosamal targeting signal found in the CD3 gamma and delta chains, is crucial for CD4 response to Nef.