Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Dev Cell. 2016 Jan 25;36(2):179-89. doi: 10.1016/j.devcel.2015.12.020.
Brush border microvilli are actin-based protrusions lining the apical surface of epithelial cells in intestines and proximal tubules of kidneys. While brush border microvilli resemble the relatively well-characterized stereocilia of hair cells, the mechanistic basis of tip-link complex organization in microvilli is poorly understood. Here, we have biochemically and structurally characterized the following pairs of interactions: protocadherin 24 and Harmonin (also known as USH1C or AIE-75), Harmonin and myosin VIIb (MYO7B), Harmonin and ANKS4B, and ANKS4B and MYO7B. We show that Harmonin, ANKS4B, and MYO7B form a stable ternary complex for anchoring microvilli tip-link cadherins. Despite having only Harmonin in common, the microvilli and the stereocilia tip-link complexes are formed via strikingly similar interaction modes. These results not only provide insight into the mechanistic bases of brush border microvilli formation and maintenance but may also be valuable for understanding some gut and/or kidney diseases caused by perturbations of brush border microvilli structures.
刷状缘微绒毛是一种肌动蛋白基的突起，排列在肠上皮细胞的顶端表面和肾脏近端小管中。虽然刷状缘微绒毛类似于相对特征明确的毛细胞的静纤毛，但微绒毛中顶链接复合物的组织机制基础理解得还很差。在这里，我们从生化和结构上对以下两对相互作用进行了表征：原钙黏蛋白 24 和 Harmonin（也称为 USH1C 或 AIE-75）、Harmonin 和肌球蛋白 VIIb（MYO7B）、Harmonin 和 ANKS4B，以及 ANKS4B 和 MYO7B。我们表明，Harmonin、ANKS4B 和 MYO7B 形成一个稳定的三元复合物，用于锚定微绒毛顶链接钙黏蛋白。尽管只有 Harmonin 是共同的，但微绒毛和静纤毛顶链接复合物的形成是通过惊人相似的相互作用模式。这些结果不仅提供了对刷状缘微绒毛形成和维持的机械基础的深入了解，而且对于理解由于刷状缘微绒毛结构的扰动引起的一些肠道和/或肾脏疾病也可能具有重要价值。
