Hair bundles are specialized for ATP delivery via creatine kinase
Hair bundles are specialized for ATP delivery via creatine kinase
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DOI：
10.1016/j.neuron.2006.12.021
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发表时间：
2007-02-01
期刊：
影响因子：
16.2
通讯作者：
Gillespie, Peter G.
中科院分区：
文献类型：
--
作者：
Shin, Jung-Bum;Streijger, Femke;Gillespie, Peter G.
当受到强烈刺激时，毛细胞的机械敏感毛束可能会过快地消耗 ATP，无法通过扩散进行补充。为了提供该束的蛋白质补充物的广泛视图，包括那些参与能量代谢的蛋白质，我们使用鸟枪质谱法来鉴定纯化的鸡前庭束的蛋白质。除了细胞骨架蛋白、参与 Ca2+ 调节的蛋白和应激反应蛋白之外，通过质谱法鉴定的许多最丰富的束蛋白也参与 ATP 合成。继β-肌动蛋白之后，肌酸激酶的胞浆脑亚型是第二丰富的束蛋白。尽管质膜 Ca2+-ATP 酶消耗 1 mM/s ATP，但在类似于 0.5 mM 的情况下，肌酸激酶仍能够维持高 ATP 水平。与发束功能中的这一关键作用一致，肌酸激酶回路对于高灵敏度听力至关重要，肌酸激酶基因敲除小鼠的听力损失证明了这一点。
When stimulated strongly, a hair cell's mechanically sensitive hair bundle may consume ATP too rapidly for replenishment by diffusion. To provide a broad view of the bundle's protein complement, including those proteins participating in energy metabolism, we used shotgun mass spectrometry methods to identify proteins of purified chicken vestibular bundles. In addition to cytoskeletal proteins, proteins involved in Ca2+ regulation, and stress-response proteins, many of the most abundant bundle proteins that were identified by mass spectrometry were involved in ATP synthesis. After beta-actin, the cytosolic brain isoform of creatine kinase was the next most abundant bundle protein; at similar to 0.5 mM, creatine kinase is capable of maintaining high ATP levels despite 1 mM/s ATP consumption by the plasma-membrane Ca2+-ATPase. Consistent with this critical role in hair bundle function, the creatine kinase circuit is essential for high-sensitivity hearing as demonstrated by hearing loss in creatine kinase knockout mice.