Rollason Ruth, Korolchuk Viktor, Hamilton Clare, Jepson Mark, Banting George
Department of Biochemistry, University of Bristol, Bristol BS8 1TD, England, UK.
J Cell Biol. 2009 Mar 9;184(5):721-36. doi: 10.1083/jcb.200804154.
CD317/tetherin is a lipid raft-associated integral membrane protein with a novel topology. It has a short N-terminal cytosolic domain, a conventional transmembrane domain, and a C-terminal glycosyl-phosphatidylinositol anchor. We now show that CD317 is expressed at the apical surface of polarized epithelial cells, where it interacts indirectly with the underlying actin cytoskeleton. CD317 is linked to the apical actin network via the proteins RICH2, EBP50, and ezrin. Knocking down expression of either CD317 or RICH2 gives rise to the same phenotype: a loss of the apical actin network with concomitant loss of apical microvilli, an increase in actin bundles at the basal surface, and a reduction in cell height without any loss of tight junctions, transepithelial resistance, or the polarized targeting of apical and basolateral membrane proteins. Thus, CD317 provides a physical link between lipid rafts and the apical actin network in polarized epithelial cells and is crucial for the maintenance of microvilli in such cells.
CD317/束缚素是一种与脂筏相关的具有新型拓扑结构的整合膜蛋白。它有一个短的N端胞质结构域、一个传统的跨膜结构域和一个C端糖基磷脂酰肌醇锚定。我们现在表明，CD317在极化上皮细胞的顶端表面表达，在那里它与下方的肌动蛋白细胞骨架间接相互作用。CD317通过RICH2、EBP50和埃兹蛋白与顶端肌动蛋白网络相连。敲低CD317或RICH2的表达会产生相同的表型：顶端肌动蛋白网络丧失，伴随顶端微绒毛丧失，基底表面肌动蛋白束增加，细胞高度降低，而紧密连接、跨上皮电阻或顶端和基底外侧膜蛋白的极化靶向没有任何损失。因此，CD317在极化上皮细胞的脂筏和顶端肌动蛋白网络之间提供了物理连接，对于维持此类细胞中的微绒毛至关重要。
