Novel calcium sensor in the outer hair cells: quantitation of oncomodulin

I. Thalmann, M. Henzl, R. Thalmann
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引用次数: 7

Abstract

The parvalbumins are small vertebrate-specific Ca 2+ -binding proteins. The mammalian α -parvalbumin is expressed in diverse cell types, including the inner hair cell, where it is proposed to serve as a cytosolic Ca 2+ buffer. By contrast, the mammalian β -parvalbumin (oncomodulin) has a highly restricted distribution and harbors a 'Ca 2+ -specific' site — properties consistent with Ca 2+ -dependent regulatory behavior. The widespread perception of oncomodulin as an oncofetal protein was recently shattered by our discovery that the protein is present in the organ of Corti. Immunohistochemical data for the rat, mouse and gerbil indicate that expression is in fact confined to the outer hair cell. We have sought to confirm and extend this work through biochemical quantitation studies on organ of Corti from rat, mouse, guinea pig and chinchilla. We find that the protein is expressed at comparably high levels (approximately 0.5 mM) in the outer hair cells in all four species. This finding contrasts sharply with the expression pattern in prenatal and neoplastic settings. We have also extended the immunohistochemical analysis to the guinea pig and performed preliminary analysis of oncomodulin mRNA levels by in situ hydridization. On the basis of our data, we suggest that the outer hair cell is the sole site of physiologically relevant oncomodulin expression. Furthermore, we propose that the protein functions in the efferent control of the electromotile response.
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外毛细胞中的新型钙传感器:肿瘤调节素的定量
细小蛋白是脊椎动物特有的ca2 +结合蛋白。哺乳动物α -小白蛋白在多种细胞类型中表达,包括内毛细胞,它被认为是细胞质ca2 +缓冲液。相比之下,哺乳动物β -小白蛋白(肿瘤调节蛋白)具有高度受限的分布,并且具有“ca2 +特异性”的位点-与ca2 +依赖的调节行为一致。人们普遍认为肿瘤调节蛋白是一种癌胎蛋白,最近我们发现这种蛋白存在于Corti器官中,这一发现打破了人们对这种蛋白的普遍认识。大鼠、小鼠和沙鼠的免疫组织化学数据表明,表达实际上仅限于外毛细胞。我们试图通过对大鼠、小鼠、豚鼠和栗鼠Corti器官的生化定量研究来证实和扩展这一工作。我们发现,在所有四个物种的外毛细胞中,该蛋白的表达水平相当高(约0.5 mM)。这一发现与产前和肿瘤环境中的表达模式形成鲜明对比。我们还将免疫组织化学分析扩展到豚鼠,并通过原位氢化对肿瘤调节素mRNA水平进行了初步分析。根据我们的数据,我们认为外毛细胞是生理上相关的肿瘤调节素表达的唯一部位。此外,我们提出该蛋白在电运动反应的传出控制中起作用。
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