Moreland K Trent, Hong Mina, Lu Wenfu, Rowley Christopher W, Ornitz David M, De Yoreo James J, Thalmann Ruediger
Department of Otolaryngology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, United States of America.
Department of Chemistry, The George Washington University, Washington, D.C., United States of America.
PLoS One. 2014 Apr 18;9(4):e95333. doi: 10.1371/journal.pone.0095333. eCollection 2014.
Otoconia are formed embryonically and are instrumental in detecting linear acceleration and gravity. Degeneration and fragmentation of otoconia in elderly patients leads to imbalance resulting in higher frequency of falls that are positively correlated with the incidence of bone fractures and death. In this work we investigate the roles otoconial proteins Otolin-1 and Otoconin 90 (OC90) perform in the formation of otoconia. We demonstrate by rotary shadowing and atomic force microscopy (AFM) experiments that Otolin-1 forms homomeric protein complexes and self-assembled networks supporting the hypothesis that Otolin-1 serves as a scaffold protein of otoconia. Our calcium carbonate crystal growth data demonstrate that Otolin-1 and OC90 modulate in vitro calcite crystal morphology but neither protein is sufficient to produce the shape of otoconia. Coadministration of these proteins produces synergistic effects on crystal morphology that contribute to morphology resembling otoconia.
耳石在胚胎期形成，对检测直线加速度和重力起重要作用。老年患者耳石的退化和破碎会导致失衡，从而使跌倒频率增加，而跌倒频率与骨折发生率和死亡率呈正相关。在这项研究中，我们调查了耳石蛋白Otolin-1和耳石素90（OC90）在耳石形成过程中所起的作用。我们通过旋转阴影和原子力显微镜（AFM）实验证明，Otolin-1形成同源蛋白复合物和自组装网络，支持了Otolin-1作为耳石支架蛋白的假说。我们的碳酸钙晶体生长数据表明，Otolin-1和OC90调节体外方解石晶体形态，但这两种蛋白都不足以产生耳石的形状。同时给予这些蛋白会对晶体形态产生协同作用，有助于形成类似耳石的形态。
