PROTEINS OF THE ORGAN OF CORTI

哺乳动物的听觉系统--灵敏度和频率无与伦比 歧视--容易受到一系列痛苦的影响， 损害声学性能。预防或治疗的关键 听力障碍存在于对听觉的透彻了解中。 转导和传递。尽管我们的技术进步很快， 理解听觉功能的机械-电气方面， 我们对潜在的大分子机制的理解仍然是 支离破碎虽然哺乳动物听觉器官的细胞， Corti器官（OC）表达数千种蛋白质，少数 与传导/传递过程直接相关。 这些分子听觉成分的详细特征将 对听觉功能有实质性的了解。OCP 1和OCP 2 在OC中具体而丰富地表达--是这个组织的成员， 精英子集在微观尺度上，OCP 2的表达模式 准确地反映了耳蜗的上皮间隙连接系统。 这种有趣的解剖学关联是否具有功能性 其重要性，或者仅仅是巧合，尚不确定。的 现有的证据表明，OCP 1和OCP 2是重要的 多蛋白调节复合物，可以想象是同一个复合物。的 确定额外的子单位是当务之急 objective. OCP-即，OCP 1、OCP 2及其相关 多肽--然后将经受一系列生化反应， 分子生物学、物理学和形态学技术。序列 来自克隆cDNA的信息将揭示潜在的位点， 用于翻译后修饰和潜在的配体结合 图案将评估这些结构特征的功能 生物化学重组OCP将通过分析 超离心、光谱学（荧光和循环光谱） 二向色性）、微量热法和NMR光谱法。表达 mRNA和蛋白质水平的OCP将作为以下因素的函数进行检查： 豚鼠、大鼠和沙鼠的年龄和发育，以及OC- 衍生细胞系。还将监测表达的变化 在OC衍生的细胞系中对环境扰动的反应， 在用正义和反义构建体转染后， OCP cDNA。OCP很可能是听觉功能障碍的目标 无论是继承还是获得。事实上，Ocp 2基因的位置 与家族性语后聋DFNAl相同 disorder.

The mammalian auditory system-- unrivaled in sensitivity and frequency discrimination -- is susceptible to a host of afflictions that compromise acoustic performance. The key to the prevention or cure of hearing disorders resides in a thorough knowledge of auditory transduction and transmission. Despite rapid advances in our understanding of the mechanico-electrical aspects of auditory function, our appreciation of the underlying macromolecular mechanisms remains fragmentary. Although the cells of the mammalian auditory organ, the organ of Corti (OC), express thousands of proteins, a small minority are directly associated with the transduction/transmission processes. Detailed characterization of these molecular auditory components will furnish substantial insight into auditory function. OCP1 and OCP2 -- expressed specifically and abundantly in the OC -- are members of this elite subset. On the microscale, OCP2 is expressed in a pattern that exactly mirrors the epithelial gap junction system of the cochlea. Whether this intriguing anatomical association has functional significance, or whether it is merely coincidental, is uncertain. The available evidence suggests that OCP1 and OCP2 are subunits of vital multi-protein regulatory complexes, conceivably the same complex. The identification of additional subunits is the immediate project objective. The OCPs -- i.e., OCP1, OCP2, and their associated polypeptides -- will then be subjected to a battery of biochemical, molecular biological, physical, and morphological techniques. Sequence information, derived from the cloned cDNAs, will reveal potential sites for post-translational modification and potential ligand-binding motifs. Functionality of these structural features will be assessed biochemically. Recombinant OCPs will be investigated by analytical ultracentrifugation, optical spectroscopy (fluorescence and circular dichroism), microcalorimetry, and NMR spectroscopy. Expression of the OCPs at the mRNA and protein levels will be examined as a function of age and development in the guinea pig, rat, and gerbil, and in OC- derived cell lines. Alterations in expression will also be monitored in OC-derived cell lines in response to environmental perturbations and following transfection with sense- and anti-sense constructions of the OCP cDNAs. The OCPs are likely targets of auditory dysfunction -- either inherited or acquired. In fact, the location of the Ocp2 gene is identical to that of DFNAl, a familial postlingual deafness disorder.