Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells.
Oncomodulin (OCM) uniquely regulates calcium signaling in neonatal cochlear outer hair cells.
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Oncomodulin（OCM）独特地调节新生儿耳蜗外毛细胞中的钙信号。
DOI：
10.1016/j.ceca.2022.102613
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发表时间：
2022-07
期刊：
影响因子：
4
通讯作者：
Simmons, Dwayne
中科院分区：
文献类型：
--
作者：
Murtha, Kaitlin E.;Yang, Yang;Ceriani, Federico;Jeng, Jing-Yi;Climer, Leslie K.;Jones, Forrest;Charles, Jack;Devana, Sai K.;Hornak, Aubrey J.;Marcotti, Walter;Simmons, Dwayne
关键词：
肿瘤调节蛋白的表达在出生后第3天开始，与耳蜗外毛细胞中钙缓冲增加相关。在耳蜗外毛细胞早期发育过程中，肿瘤调节蛋白的缺失改变了α-小清蛋白和sorcin的表达模式。肿瘤调节蛋白和α-小清蛋白都有助于出生后早期发育过程中OHC的钙稳态。当在HEK 293 T细胞中瞬时表达时，小清蛋白或sorcin在耳蜗外毛细胞（OHC）中，Ca 2+通道、泵和Ca 2+结合蛋白（CaBP）的网络调节游离Ca 2+离子的定位、扩散和大小。在出生后早期发育过程中，OHC表达三种显著的移动的EF-手型CaBP：肿瘤调节蛋白（OCM）、α-小清蛋白（APV）和sorcin。我们以前已经表明，Ocm（Ocm-/-）的缺失引起进行性耳蜗功能障碍的年轻成年小鼠。在这里，我们表明，Ca 2+信号的变化开始早期出生后的发展OCM-/-小鼠。虽然突变OHC表现出正常的电生理曲线相比，控制，其细胞内的Ca 2+信号被改变。出生后第3天（P3）OCM表达的开始导致KCl诱导的OHC中Ca 2+瞬变的发育变化，并导致KCl诱导的Ca 2+瞬变比OCM-/-同窝仔细胞中引起的更慢。我们在动物模型和培养细胞中比较了OCM与其他CaBP的缓冲动力学。在Ocm和Apv的双敲除（Ocm-/-;Apv-/-）中，突变OHC显示更快的Ca 2+动力学，表明APV也可能有助于出生后早期的Ca 2+信号传导。在转染的HEK 293 T细胞中，OCM比APV或sorcin更能减缓Ca 2+动力学。我们的结论是，OCM控制细胞内的Ca 2+环境，通过降低OHC和转染的HEK 293 T细胞中的自由可用的[Ca 2 +]i的量。我们认为OCM通过其独特的Ca 2+缓冲能力在塑造早期OHC Ca 2+信号的发展中起着重要作用。
Onset of oncomodulin expression occurs at postnatal day 3, which correlates with increased calcium buffering in cochlear outer hair cells Deletion of oncomodulin alters the expression patterns of α-parvalbumin and sorcin during early development of outer hair cells Oncomodulin and α-parvalbumin both contribute to OHC calcium homeostasis during early postnatal development Oncomodulin exhibits faster calcium-buffering compared to either α-parvalbumin or sorcin when transiently expressed in HEK293T cells In cochlear outer hair cells (OHCs), a network of Ca2+ channels, pumps and Ca2+-binding proteins (CaBPs) regulates the localization, spread, and magnitude of free Ca2+ ions. During early postnatal development, OHCs express three prominent mobile EF-hand CaBPs: oncomodulin (OCM), α-parvalbumin (APV) and sorcin. We have previously shown that deletion of Ocm (Ocm-/-) gives rise to progressive cochlear dysfunction in young adult mice. Here, we show that changes in Ca2+ signaling begin early in postnatal development of Ocm-/- mice. While mutant OHCs exhibit normal electrophysiological profiles compared to controls, their intracellular Ca2+ signaling is altered. The onset of OCM expression at postnatal day 3 (P3) causes a developmental change in KCl-induced Ca2+ transients in OHCs and leads to slower KCl-induced Ca2+ transients than those elicited in cells from Ocm-/- littermates. We compared OCM buffering kinetics with other CaBPs in animal models and cultured cells. In a double knockout of Ocm and Apv (Ocm-/-;Apv-/-), mutant OHCs show even faster Ca2+ kinetics, suggesting that APV may also contribute to early postnatal Ca2+ signaling. In transfected HEK293T cells, OCM slows Ca2+ kinetics more so than either APV or sorcin. We conclude that OCM controls the intracellular Ca2+ environment by lowering the amount of freely available [Ca2+]i in OHCs and transfected HEK293T cells. We propose that OCM plays an important role in shaping the development of early OHC Ca2+ signals through its inimitable Ca2+ buffering capacity.
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DOI：
10.1113/jp279795
发表时间：
2020-09
期刊：
The Journal of physiology
影响因子：
--
作者：
Jeng JY;Johnson SL;Carlton AJ;De Tomasi L;Goodyear RJ;De Faveri F;Furness DN;Wells S;Brown SDM;Holley MC;Richardson GP;Mustapha M;Bowl MR;Marcotti W
通讯作者：
Marcotti W
影响因子：
4.6
作者：
Ilari A;Fiorillo A;Poser E;Lalioti VS;Sundell GN;Ivarsson Y;Genovese I;Colotti G
通讯作者：
Colotti G
影响因子：
16.6
作者：
Corns LF;Johnson SL;Roberts T;Ranatunga KM;Hendry A;Ceriani F;Safieddine S;Steel KP;Forge A;Petit C;Furness DN;Kros CJ;Marcotti W
通讯作者：
Marcotti W
DOI：
10.1186/1478-811x-10-20
发表时间：
2012-07-12
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Ceriani F;Mammano F
通讯作者：
Mammano F
影响因子：
64.8
作者：
HOTH, M;PENNER, R
通讯作者：
PENNER, R