Legg J W, Isacke C M
Department of Biology, Imperial College of Science, Technology and Medicine, London, UK.
Curr Biol. 1998 Jun 4;8(12):705-8. doi: 10.1016/s0960-9822(98)70277-5.
ERM (ezrin, radixin and moesin) proteins function as linkers between the actin cytoskeleton and the plasma membrane. In addition to this structural role, these proteins are highly regulatable making them ideal candidates to mediate important physiological events such as adhesion and membrane morphology and to control formation and breakdown of membrane-cytoskeletal junctions. Recently, a direct interaction in vitro has been demonstrated between ERM proteins and the hyaluronan receptor, CD44. We have mapped the ezrin-binding site to two clusters of basic amino acids in a membrane-proximal 9 amino-acid region within the CD44 cytoplasmic domain. To investigate the functional importance of this interaction in vivo, we created a number of mutations within full-length CD44 and expressed these mutants in human melanoma cells. We demonstrate here that mutations within the ezrin-binding site do not disrupt the plasma membrane localization of CD44 and, in addition, that this region is not required to mediate efficient hyaluronan binding. These studies suggest that ERM proteins mediate the outside-in, rather than inside-out, signalling of adhesion receptors.
ERM（埃兹蛋白、根蛋白和膜突蛋白）家族蛋白作为肌动蛋白细胞骨架与质膜之间的连接蛋白发挥作用。除了这一结构功能外，这些蛋白具有高度可调节性，使其成为介导诸如黏附、膜形态等重要生理过程以及控制膜 - 细胞骨架连接的形成与分解的理想候选蛋白。最近，已证实在体外ERM蛋白与透明质酸受体CD44之间存在直接相互作用。我们已将埃兹蛋白结合位点定位至CD44胞质结构域内靠近膜的9个氨基酸区域中的两个碱性氨基酸簇。为了研究这种相互作用在体内的功能重要性，我们在全长CD44内产生了多个突变，并在人黑色素瘤细胞中表达这些突变体。我们在此证明，埃兹蛋白结合位点内的突变不会破坏CD44的质膜定位，此外，该区域对于介导有效的透明质酸结合并非必需。这些研究表明，ERM蛋白介导黏附受体的外向内而非内向外交联信号传导。
