Shoham Tsipi, Rajapaksa Ranjani, Kuo Chiung-Chi, Haimovich Joseph, Levy Shoshana
Department of Medicine, Division of Oncology, CCSR Room 1105a, 269 Campus Drive, Stanford University Medical Center, Stanford, CA 94305-5151, USA.
Mol Cell Biol. 2006 Feb;26(4):1373-85. doi: 10.1128/MCB.26.4.1373-1385.2006.
The tetraspanin web is composed of a network of tetraspanins and their partner proteins that facilitate cellular interactions and fusion events by an unknown mechanism. Our aim was to unravel the web partnership between the tetraspanin CD81 and CD19, a cell surface signaling molecule in B lymphocytes. We found that CD81 plays multiple roles in the processing, intracellular trafficking, and membrane functions of CD19. Surprisingly, these different roles are embodied in distinct CD81 domains, which function in the different cellular compartments: the N-terminal tail of CD81 has an effect on the glycosylation of CD19; the first transmembrane domain of CD81 is sufficient to support the exit of CD19 from the endoplasmic reticulum, although the large extracellular loop (LEL) of CD81 associates physically with CD19 early during biosynthesis; and finally, the TM2 and TM3 domains of CD81 play a role in the transmission of signals initiated upon engagement of the LEL. The participation of distinct CD81 domains in varied functions may explain the pleiotropic effects of CD81 within the tetraspanin web.
四跨膜蛋白网络由四跨膜蛋白及其伴侣蛋白组成的网络构成，其通过未知机制促进细胞间相互作用和融合事件。我们的目的是揭示四跨膜蛋白CD81与CD19（B淋巴细胞中的一种细胞表面信号分子）之间的网络伙伴关系。我们发现CD81在CD19的加工、细胞内运输和膜功能中发挥多种作用。令人惊讶的是，这些不同的作用体现在不同的CD81结构域中，它们在不同的细胞区室中发挥作用：CD81的N末端尾巴对CD19的糖基化有影响；CD81的第一个跨膜结构域足以支持CD19从内质网中输出，尽管CD81的大细胞外环（LEL）在生物合成早期就与CD19发生物理结合；最后，CD81的TM2和TM3结构域在LEL结合引发的信号传递中发挥作用。不同的CD81结构域参与多种功能可能解释了CD81在四跨膜蛋白网络中的多效性作用。
