Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Dev Cell. 2010 Nov 16;19(5):727-39. doi: 10.1016/j.devcel.2010.10.008.
The neurofibromatosis type 2 (NF2) tumor suppressor, Merlin, is a FERM (Four point one, Ezrin, Radixin, Moesin) domain-containing protein whose loss results in defective morphogenesis and tumorigenesis in multiple tissues. Like the closely related ERM proteins (Ezrin, Radixin, and Moesin), Merlin may organize the plasma membrane by assembling membrane protein complexes and linking them to the cortical actin cytoskeleton. We previously found that Merlin is a critical mediator of contact-dependent inhibition of proliferation and is required for the establishment of stable adherens junctions (AJs) in cultured cells. Here, we delineate the molecular function of Merlin in AJ establishment in epidermal keratinocytes in vitro and confirm that a role in AJ establishment is an essential function of Merlin in vivo. Our studies reveal that Merlin can associate directly with α-catenin and link it to Par3, thereby providing an essential link between the AJ and the Par3 polarity complex during junctional maturation.
神经纤维瘤病 2 型 (NF2) 肿瘤抑制因子 Merlin 是一种 FERM（Four point one，Ezrin，Radixin，Moesin）结构域蛋白，其缺失会导致多种组织的形态发生缺陷和肿瘤发生。像密切相关的 ERM 蛋白（Ezrin、Radixin 和 Moesin）一样，Merlin 可能通过组装膜蛋白复合物并将它们连接到皮质肌动球蛋白细胞骨架上来组织质膜。我们之前发现 Merlin 是接触依赖性抑制增殖的关键介质，并且是培养细胞中稳定粘着连接 (AJ) 建立所必需的。在这里，我们描述了 Merlin 在体外表皮角质形成细胞 AJ 建立中的分子功能，并证实了在 AJ 建立中的作用是 Merlin 在体内的一个基本功能。我们的研究表明，Merlin 可以直接与 α-连环蛋白结合，并将其与 Par3 连接，从而在连接成熟过程中为 AJ 和 Par3 极性复合物之间提供了一个必要的连接。
