Center of Bioscience, - Institute for Molecular Physiology and Genetics , Bratislava, Slovakia.
Faculty of Natural Sciences, University of Ss. Cyril and Methodius , Trnava, Slovakia.
Channels (Austin). 2020 Dec;14(1):380-392. doi: 10.1080/19336950.2020.1831328.
Voltage-gated Ca channels are typically integrated in a complex network of protein-protein-interactions, also referred to as Ca channel nanodomains. Amongst the neuronal Ca2 channel family, Ca2.2 is of particular importance due to its general role for signal transmission from the periphery to the central nervous system, but also due to its significance for pain perception. Thus, Ca2.2 is an ideal target candidate to search for pharmacological inhibitors but also for novel modulatory interactors. In this review we summarize the last years findings of our intense screenings and characterization of the six Ca2.2 interaction partners, tetraspanin-13 (TSPAN-13), reticulon 1 (RTN1), member 1 of solute carrier family 38 (SLC38), prostaglandin D2 synthase (PTGDS), transmembrane protein 223 (TMEM223), and transmembrane BAX inhibitor motif 3 (Grina/TMBIM3) containing protein. Each protein shows a unique way of channel modulation as shown by extensive electrophysiological studies. Amongst the newly identified interactors, Grina/TMBIM3 is most striking due to its modulatory effect which is rather comparable to G-protein regulation.
电压门控钙通道通常整合在蛋白质-蛋白质相互作用的复杂网络中，也称为钙通道纳米域。在神经元钙通道家族中，钙通道亚基 2.2 因其在从外周向中枢神经系统传递信号方面的普遍作用而尤为重要，但也因其在疼痛感知中的重要性而重要。因此，钙通道 2.2 是寻找药理学抑制剂的理想候选目标，也是寻找新型调节相互作用因子的理想候选目标。在这篇综述中，我们总结了过去几年我们对钙通道 2.2 的六个相互作用伙伴（四跨膜蛋白 13（TSPAN-13）、内质网 1（RTN1）、溶质载体家族 38 成员 1（SLC38）、前列腺素 D2 合酶（PTGDS）、跨膜蛋白 223（TMEM223）和包含膜 BAX 抑制剂基序 3（Grina/TMBIM3）的蛋白）的密集筛选和特性分析的最新发现。每个蛋白都通过广泛的电生理研究显示出独特的通道调节方式。在新鉴定的相互作用因子中，Grina/TMBIM3 最为引人注目，因为其调节作用与 G 蛋白调节相当。
