Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
MGS/RSMAS and UMCAM/Chemistry, University of Miami, Coral Gables, FL, 33146, USA.
J Mol Med (Berl). 2018 Nov;96(11):1227-1238. doi: 10.1007/s00109-018-1694-x. Epub 2018 Oct 3.
RIPOR2 (previously known as FAM65B) localizes to stereocilia of auditory hair cells and causes deafness when its function is disturbed by mutations. Here, we demonstrate that during the morphogenesis of the hair cell bundle, absence of Ripor2 affects the orientation of this key subcellular structure. We show that Ripor2 interacts with Myh9, a protein encoded by a known deafness gene. Absence of Ripor2 is associated with low Myh9 abundance in the mouse cochlea despite increased amount of Myh9 transcripts. While Myh9 is mainly expressed in stereocilia, a phosphorylated form of Myh9 is particularly enriched in the kinocilium. In Ripor2-deficient mice, kinocilium shows an aberrant localization which associates with a reduced content of phosphorylated Myh9. Acetylated alpha tubulin, another specific kinociliary protein which contributes to microtubule stabilization, is reduced in the absence of Ripor2 as well. We propose that Ripor2 deficiency influences abundance and/or post-translational modifications of proteins expressed in both stereocilia and kinocilia. This effect may have a negative impact on the structure and function of the auditory hair cell bundle.
RIPOR2（以前称为 FAM65B）定位于听觉毛细胞的静纤毛，当其功能因突变而受到干扰时会导致耳聋。在这里，我们证明了在毛细胞束的形态发生过程中，Ripor2 的缺失会影响这个关键亚细胞结构的取向。我们表明 Ripor2 与 Myh9 相互作用，Myh9 是一个已知耳聋基因的编码蛋白。尽管 Myh9 转录本的数量增加，但 Ripor2 缺失的小鼠耳蜗中 Myh9 的丰度较低。虽然 Myh9 主要在静纤毛中表达，但磷酸化形式的 Myh9 在纤毛中特别丰富。在 Ripor2 缺陷型小鼠中，纤毛出现异常定位，与磷酸化 Myh9 含量减少有关。乙酰化的α微管蛋白是另一种稳定微管的特异性纤毛蛋白，在 Ripor2 缺失时也减少。我们提出，Ripor2 缺乏会影响静纤毛和纤毛中表达的蛋白质的丰度和/或翻译后修饰。这种影响可能对听觉毛细胞束的结构和功能产生负面影响。
