Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
J Immunol. 2010 Apr 1;184(7):3689-96. doi: 10.4049/jimmunol.0902075. Epub 2010 Mar 5.
Membrane rafts and signaling molecules associated with them are thought to play important roles in immunoreceptor signaling. Rafts differ in their lipid and protein compositions from the rest of the membrane and are relatively resistant to solubilization by Triton X-100 or similar detergents, producing buoyant, detergent-resistant membranes (DRMs) that can be isolated by density gradient ultracentrifugation. One of the key signaling molecules present in T cell DRMs is the transmembrane adaptor protein LAT (linker for activation of T cells). In contrast to previous results, a recent study demonstrated that a LAT construct not present in the buoyant DRMs is fully able to support TCR signaling and development of T cells in vivo. This finding caused doubts about the real physiological role of rafts in TCR signaling. In this study, we demonstrate that these results can be explained by the existence of a novel type of membrane raft-like microdomains, producing upon detergent solubilization "heavy DRMs" containing a number of membrane molecules. At a moderate level of expression, LAT supported TCR signaling more efficiently than constructs targeted to the microdomains producing heavy DRMs or to nonraft membrane. We suggest that different types of membrane microdomains provide environments regulating the functional efficiencies of signaling molecules present therein.
膜筏及其相关的信号分子被认为在免疫受体信号转导中发挥重要作用。筏与膜的其余部分在脂质和蛋白质组成上有所不同，并且相对不易被 Triton X-100 或类似去污剂溶解，产生浮力大、去污剂抗性的膜（DRM），可通过密度梯度超速离心分离。T 细胞 DRM 中存在的一种关键信号分子是跨膜衔接蛋白 LAT（T 细胞激活的衔接蛋白）。与先前的结果相反，最近的一项研究表明，一种不在浮力 DRM 中的 LAT 构建体完全能够支持 TCR 信号转导和体内 T 细胞的发育。这一发现使人对筏在 TCR 信号转导中的真正生理作用产生了怀疑。在这项研究中，我们证明这些结果可以通过存在一种新型的膜筏样微域来解释，这种微域在去污剂溶解后产生含有许多膜分子的“重 DRM”。在适度的表达水平上，LAT 支持 TCR 信号转导的效率比靶向产生重 DRM 的微域或非筏膜的构建体更高。我们认为，不同类型的膜微域提供了调节其中存在的信号分子功能效率的环境。
