Rab3a-Bound CD63 Is Degraded and Rab3a-Free CD63 Is Incorporated into HIV-1 Particles.
Rab3a-Bound CD63 Is Degraded and Rab3a-Free CD63 Is Incorporated into HIV-1 Particles.
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DOI：
10.3389/fmicb.2017.01653
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发表时间：
2017
影响因子：
5.2
通讯作者：
Matsuyama T
中科院分区：
文献类型：
--
作者：
Kubo Y;Masumoto H;Izumida M;Kakoki K;Hayashi H;Matsuyama T
CD 63是四跨膜蛋白家族的成员，参与人类免疫缺陷病毒1型（HIV-1）的病毒体产生，但其机制尚不清楚。在这项研究中，我们发现一种小的GTP结合蛋白Rab 3a与CD 63相互作用。当Rab 3a外源性表达时，细胞中CD 63的量减少。Rab 3a介导的CD 63减少被溶酶体和蛋白酶体抑制剂抑制。通过使用特异性shRNA降低内源性Rab 3a水平来增加CD 63的量。这些结果表明Rab 3a与CD 63结合以诱导CD 63的降解。Rab 3a被认为参与胞吐，但我们发现Rab 3a的另一个功能影响溶酶体中CD 63的命运。CD 63与Rab 3a相互作用并掺入HIV-1颗粒中。然而，Rab 3a在HIV-1病毒体中未检测到，从而表明不含Rab 3a的CD 63，而不是Rab 3a结合的CD 63，被掺入HIV-1颗粒中。Rab 3a的过表达或沉默适度减少HIV-1病毒体形成。Rab 3a的过表达降低了CD 63的水平，但不影响CD 63掺入HIV-1颗粒。该研究表明Rab 3a与CD 63结合以诱导CD 63降解，并且只有不含Rab 3a的CD 63掺入HIV-1颗粒中。
CD63, a member of the tetraspanin family, is involved in virion production by human immunodeficiency virus type 1 (HIV-1), but its mechanism is unknown. In this study, we showed that a small GTP-binding protein, Rab3a, interacts with CD63. When Rab3a was exogenously expressed, the amounts of CD63 decreased in cells. The Rab3a-mediated reduction of CD63 was suppressed by lysosomal and proteasomal inhibitors. The amount of CD63 was increased by reducing the endogenous Rab3a level using a specific shRNA. These results indicate that Rab3a binds to CD63 to induce the degradation of CD63. Rab3a is thought to be involved in exocytosis, but we found that another function of Rab3a affects the fate of CD63 in lysosomes. CD63 interacted with Rab3a and was incorporated into HIV-1 particles. However, Rab3a was not detected in HIV-1 virions, thereby indicating that Rab3a-free CD63, but not Rab3a-bound CD63, is incorporated into HIV-1 particles. Overexpression or silencing of Rab3a moderately reduced HIV-1 virion formation. Overexpression of Rab3a decreased CD63 levels, but did not affect the incorporation of CD63 into HIV-1 particles. This study showed that Rab3a binds to CD63 to induce the degradation of CD63, and only Rab3a-free CD63 is incorporated into HIV-1 particles.