CDK5 interacts with Slo and affects its surface expression and kinetics through direct phosphorylation.
CDK5 interacts with Slo and affects its surface expression and kinetics through direct phosphorylation.
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DOI：
10.1152/ajpcell.00339.2011
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发表时间：
2012-03
期刊：
影响因子：
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通讯作者：
J. Bai;Alexei A. Surguchev;Powrnima Joshi;Liza Gross;D. Navaratnam
中科院分区：
文献类型：
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作者：
J. Bai;Alexei A. Surguchev;Powrnima Joshi;Liza Gross;D. Navaratnam
大电导钙活化钾（BK）通道普遍存在，并在许多疾病中发挥重要作用。在耳毛细胞中，它们在电子调谐中起着关键作用，这是一种频率识别机制。这些通道表现出可变的动力学和沿张力轴的表达。尽管其在毛细胞中功能的分子基础尚不清楚，但已经确定BK通道由成孔α-亚基（Slo）和一些辅助亚基组成。在这里，我们确定了周期蛋白依赖性激酶家族的成员CDK5作为Slo的相互作用伙伴。我们发现CDK5存在于毛细胞中，并在角质层板和周长区高浓度表达。在人胚胎肾细胞中，我们发现CDK5通过直接磷酸化Slo来抑制Slo的表面表达。同样，我们注意到CDK5通过T847的直接磷酸化影响慢电压激活和失活动力学。这些数据表明，CDK5可能在毛细胞的电调谐和Slo的表面表达中起关键作用。
Large-conductance calcium-activated potassium (BK) channels are ubiquitous and play an important role in a number of diseases. In hair cells of the ear, they play a critical role in electrical tuning, a mechanism of frequency discrimination. These channels show variable kinetics and expression along the tonotopic axis. Although the molecular underpinnings to its function in hair cells are poorly understood, it is established that BK channels consist of a pore-forming α-subunit (Slo) and a number of accessory subunits. Here we identify CDK5, a member of the cyclin-dependent kinase family, as an interacting partner of Slo. We show CDK5 to be present in hair cells and expressed in high concentrations in the cuticular plate and in the circumferential zone. In human embryonic kidney cells, we show that CDK5 inhibits surface expression of Slo by direct phosphorylation of Slo. Similarly, we note that CDK5 affects Slo voltage activation and deactivation kinetics, by a direct phosphorylation of T847. Taken together with its increasing expression along the tonotopic axis, these data suggest that CDK5 likely plays a critical role in electrical tuning and surface expression of Slo in hair cells.