Oncomodulin regulates spontaneous calcium signalling and maturation of afferent innervation in cochlear outer hair cells.
Oncomodulin regulates spontaneous calcium signalling and maturation of afferent innervation in cochlear outer hair cells.
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DOI：
10.1113/jp284690
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发表时间：
2023-10
影响因子：
5.5
通讯作者：
Simmons, Dwayne D.
中科院分区：
文献类型：
--
作者：
Yang, Yang;Murtha, Kaitlin;Climer, Leslie K.;Ceriani, Federico;Thompson, Pierce;Hornak, Aubrey J.;Marcotti, Walter;Simmons, Dwayne D.
关键词：
耳蜗外毛细胞 (OHC) 负责哺乳动物听觉的精确频率选择性和敏感性。在发育过程中，OHC 传入连接的成熟通过感觉细胞和非感觉细胞中协调的自发 Ca2+ 活动来完善。新生儿 OHC 中的钙信号传导可以通过癌调节蛋白（OCM，β-小清蛋白）（一种 EF 手钙结合蛋白）进行调节。在这里，我们研究了 OCM 是否在发育过程中调节 OHC 自发 Ca2+ 活性和传入连接。使用在野生型 (Ocm+/+) 和 Ocm 敲除 (Ocm−/−) 同窝仔鼠的 OHC 中表达的基因编码 Ca2+ 传感器 (GCaMP6s)，我们发现出生后 Ocm−/− 耳蜗的 OHC 中自发 Ca2+ 活性增加，嘌呤能受体上调。在没有 OCM 的情况下，OHC 的传入突触成熟被延迟，导致听力出现前 Ocm−/− OHC 上的带状突触和传入纤维数量增加。我们认为 OCM 调节发育中耳蜗中的自发 Ca2+ 信号传导和 OHC 传入神经支配的成熟。
Cochlear outer hair cells (OHCs) are responsible for the exquisite frequency selectivity and sensitivity of mammalian hearing. During development, the maturation of OHC afferent connectivity is refined by coordinated spontaneous Ca2+ activity in both sensory and non-sensory cells. Calcium signaling in neonatal OHCs can be modulated by oncomodulin (OCM, β-parvalbumin), an EF-hand calcium-binding protein. Here, we investigated whether OCM regulates OHC spontaneous Ca2+ activity and afferent connectivity during development. Using a genetically encoded Ca2+ sensor (GCaMP6s) expressed in OHCs in wild-type (Ocm+/+) and Ocm knockout (Ocm−/−) littermates, we found increased spontaneous Ca2+ activity and upregulation of purinergic receptors in OHCs from Ocm−/− cochlea immediately following birth. The afferent synaptic maturation of OHCs was delayed in the absence of OCM, leading to an increased number of ribbon synapses and afferent fibers on Ocm−/− OHCs before hearing onset. We propose that OCM regulates the spontaneous Ca2+ signaling in the developing cochlea and the maturation of OHC afferent innervation.
影响因子：
4.8
作者：
Zuccotti A;Lee SC;Campanelli D;Singer W;Satheesh SV;Patriarchi T;Geisler HS;Köpschall I;Rohbock K;Nothwang HG;Hu J;Hell JW;Schimmang T;Rüttiger L;Knipper M
通讯作者：
Knipper M
影响因子：
4.8
作者：
Sander, Simon;Mueller, Isabel;Garcia-Alai, Maria M.;Nicke, Annette;Tidow, Henning
通讯作者：
Tidow, Henning