The tetraspan protein EMP2 regulates expression of caveolin-1
The tetraspan protein EMP2 regulates expression of caveolin-1
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DOI：
10.1074/jbc.m702117200
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发表时间：
2007-09-07
影响因子：
4.8
通讯作者：
Braun, Jonathan
中科院分区：
文献类型：
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作者：
Forbes, Ashley;Wadehra, Madhuri;Braun, Jonathan
小窝蛋白-1是小窝的主要成分，在细胞内的多种活动中发挥作用，包括膜运输和信号转导。EMP 2（epithelial membrane protein 2，上皮膜蛋白2）是一种新发现的调节小窝蛋白-1（caveolin-1）表达的蛋白质。在这项研究中，我们分析了EMP 2介导的小窝蛋白-1调节的机制。在NIH 3 T3细胞和人视网膜色素上皮细胞系（ARPE-19）中，EMP 2调节小窝蛋白-1的转录，更重要的是调节其蛋白水平。EMP 2介导的小窝蛋白-1下调不影响小窝蛋白-1的翻译效率、磷酸化或蛋白酶体介导的降解。对小窝蛋白-1蛋白半衰期的分析表明，EMP 2介导的小窝蛋白-1的损失迅速发生。蛋白酶抑制和激光共聚焦显微镜关联这种命运与特定的细胞内区室化，包括早期溶酶体交付。这些发现阐明了小窝蛋白-1调节的新机制，并定义了EMP 2作为细胞膜组成的关键调节因子的额外作用。
Caveolin-1 is the primary component of caveolae and functions in a variety of intracellular activities, including membrane trafficking and signal transduction. EMP2(epithelial membrane protein 2) is a tetraspan protein recently identified as a novel regulator of caveolin-1 expression. In this study, we analyzed the mechanism of EMP2-mediated caveolin-1 regulation. In NIH 3T3 cells and in the human retinal pigment epithelium cell line (ARPE-19), EMP2 regulates caveolin-1 transcription and more substantially its protein levels. EMP2-mediated down-regulation of caveolin-1 does not affect caveolin-1 translational efficiency, phosphorylation, or proteasome-mediated degradation. Analysis of caveolin-1 protein half-life indicates the EMP2-mediated loss of caveolin-1 occurs rapidly. Protease inhibition and laser confocal microscopy associates this fate with specific intracellular compartmentalization, including early lysosomal delivery. These findings elucidate a new mechanism of caveolin-1 regulation and define an additional role for EMP2 as a key regulator of cell membrane composition.