Different properties and cooperative effects of calmodulin N-and Clobes in regulations of Cav1.2 channel
作者单位：Department of Pharmaceutical Toxicology School of Pharmacy China Medical University Department of Physiology Graduate School of Medical and Dental Sciences Kagoshima University
会议名称：《第十一届全国钙信号和细胞功能研讨会》
会议日期：2016年
学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0901[农学-作物学] 090102[农学-作物遗传育种]
摘 要：Voltage-gated Ca channels(Cavs) are regulated by Ca/calmodulin(Ca M) through two opposing feedback mechanisms, Ca-dependent facilitation(CDF) and inactivation(CDI). A Ca M molecule consists of two connected lobes, the N-terminal lobe(N-lobe) and the C-terminal lobe(C-lobe). It is currently quite controversial whether the two lobes of Ca M mediate the opposing feedback systems independently. By using Ca M N-and C-lobe fragments, we confirmed that the N-lobe was bound to the IQ motif, a Ca M-binding site on the C-terminus of Cav1.2 in free or low Ca conditions, revealing that N-lobe played a more important role when intracellular Ca concentration is free or low. While, neither individual N-lobe nor C-lobe but equimolar mixture of N-and C-lobe(N&C) could induce CDI under our experimental condition, indicating that CDI is a process that starts by the binding of the single N-lobe to the channel and ends with the co-existence of N-and C-lobes. The binding affinities of the individual lobes were much lower than that of the full-structured Ca M, implying that the linker may contribute to the effective cooperation between the N-and C-lobes. We propose a model wherein the CDI process is akin to double touching magic locks controlled by N-and C-lobe bindings, which provides an important perspective to understand the regulatory mechanisms of Cavs and the control of intracellular Ca homeostasis.