Maddala Rupalatha, Walters Mark, Brophy Peter J, Bennett Vann, Rao Ponugoti V
Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina;
Department of Mechanical Engineering and Materials Science, Pratt School of Engineering, Duke University, Durham, North Carolina;
Am J Physiol Cell Physiol. 2016 Jan 15;310(2):C115-26. doi: 10.1152/ajpcell.00111.2015. Epub 2015 Nov 4.
Periaxin (Prx), a PDZ domain protein expressed preferentially in myelinating Schwann cells and lens fibers, plays a key role in membrane scaffolding and cytoarchitecture. Little is known, however, about how Prx is anchored to the plasma membrane. Here we report that ankyrin-B (AnkB), a well-characterized adaptor protein involved in linking the spectrin-actin cytoskeleton to integral membrane proteins, is required for membrane association of Prx in lens fibers and colocalizes with Prx in hexagonal fiber cells. Under AnkB haploinsufficiency, Prx accumulates in the soluble fraction with a concomitant loss from the membrane-enriched fraction of mouse lenses. Moreover, AnkB haploinsufficiency induced age-dependent disruptions in fiber cell hexagonal geometry and radial alignment and decreased compressive stiffness in mouse lenses parallel to the changes observed in Prx null mouse lens. Both AnkB- and Prx-deficient mice exhibit disruptions in membrane organization of the spectrin-actin network and the dystrophin-glycoprotein complex in lens fiber cells. Taken together, these observations reveal that AnkB is required for Prx membrane anchoring and for maintenance of lens fiber cell hexagonal geometry, membrane skeleton organization, and biomechanics.
外周蛋白（Prx）是一种主要在髓鞘形成雪旺细胞和晶状体纤维中表达的PDZ结构域蛋白，在膜支架和细胞结构中起关键作用。然而，关于Prx如何锚定到质膜上却知之甚少。在此，我们报告锚蛋白B（AnkB），一种参与将血影蛋白 - 肌动蛋白细胞骨架与整合膜蛋白连接的特征明确的衔接蛋白，是Prx在晶状体纤维中与膜结合所必需的，并且在六边形纤维细胞中与Prx共定位。在AnkB单倍剂量不足的情况下，Prx在可溶性部分积累，同时从小鼠晶状体富含膜的部分丢失。此外，AnkB单倍剂量不足诱导了与Prx基因敲除小鼠晶状体中观察到的变化平行的、与年龄相关的纤维细胞六边形几何形状和径向排列的破坏以及小鼠晶状体压缩硬度的降低。AnkB和Prx缺陷型小鼠在晶状体纤维细胞膜组织中血影蛋白 - 肌动蛋白网络和肌营养不良蛋白 - 糖蛋白复合物均表现出破坏。综上所述，这些观察结果表明，AnkB是Prx膜锚定以及维持晶状体纤维细胞六边形几何形状、膜骨架组织和生物力学所必需的。
