Ca^<2+> channelplexes : assembly in the membrane and physiological significance

Ca^<2+>作为第二信使控制着各种各样的生物反应，并有助于骨骼等组织的形成，从而在调节全身、组织和细胞水平的“稳态”中发挥核心作用。在我的研究中，我专注于电压依赖性Ca^<2+>通道（VDCCs）和瞬态受体电位（TRP）通道，旨在了解Ca^<2+>通道蛋白复合物（Ca^<2+>通道丛）生物膜形成和组装的机制，以及它们的生理意义。首先，我揭示了几种独特的激活机制，这些机制调节了TRP Ca^<2+>-渗透性阳离子通道的细胞信号转导。其次，我已经证明通道蛋白不仅作为Ca^<2+>渗透装置，而且作为受体、信号调节蛋白和支架蛋白的组装中心。第三，Ca^<2+>通道蛋白复合物在信号转导过程中通过反馈调节通路的形成发挥了重要作用。最后，我也证明了Ca^<2+>通道丛在组织水平上的生理意义。B淋巴细胞活化中的TRPC3通道丛和突触前囊泡融合中的P/Q型vdcomplex是本研究结果的例子。因此，我的研究阐明了单个Ca^<2+>通道如何在独特的细胞反应中发挥作用。

Ca^<2+> as a second messenger controls a wide variety of biological responses and contributes to formation of tissues such as bones, thereby playing a central role in regulating "homeostasis" at whole body, tissue, and cell levels. In my research, I have focused on voltage-dependent Ca^<2+> channels (VDCCs) and transient receptor potential (TRP) channels to aim at understanding mechanisms, that underlie formation and assembly at the biomembrane of Ca^<2+> channel protein complexes (Ca^<2+> channelplexes), and their physiological significance. Firstly, I have unveiled several unique activation mechanisms, that regulate cellular signal transduction for TRP Ca^<2+>-permeable caion channels. Secondly, I have demonstrated that channel proteins act not only as Ca^<2+>-permeating apparatus but also as assembly centers for receptors, signal-regulating proteins, and scaffolding proteins. Thirdly, important roles of Ca^<2+> channel protein complexes via formation of feedback regulation pathways in signal transduction have been demonstrated. Finally, I have also shown physiological significance of Ca^<2+> channelplexes at tissue levels. TRPC3 channelplexes in B lymphocyte activation and P/Q type VDCCplexes in presynaptic vesicle fusion are examples of the outcome of this study. Thus, my study clarifies how individual Ca^<2+> channels play roles in unique cellular responses.