Calcium Activated K+ Channels in Brain

描述(申请人提供)：单一类别的蛋白质--离子 通道-是神经元信号特性的主要决定因素，而 这个实验室的长期目标是确定所做的贡献 通过不同类别的离子通道来影响神经元的信号特性。 我们目前的重点是一系列钾通道，即钙激活的钾 因为1)它们几乎存在于所有神经元中，也存在于许多神经元中 非神经细胞，2)它们在这些不同的 小区类型，以及3)这些通道的属性在不同的 由于异四聚体的联合而产生的细胞环境，可供选择 剪接，与其他辅助蛋白结合，并通过秒调节 信使级联。我们的具体目标是： 1)确定并表征候选缔合结构域和四聚结构域 在KCA频道。我们将测试KCA通道包含特定的 促进某些蛋白质四聚的蛋白质结构域，以及排除 其他亚单位。 2)识别和表征分子间KCA通道结合结构域，以及 由此产生的蛋白质复合体。我们将检验KCA通道的假设 A-亚基含有促进分子间结合的蛋白质结构域 其他蛋白质到KCA通道的四聚体导致新的KCA通道 表型。 3)确定KCA通道α-亚基的选择性剪接在 蛋白质复合体的形成。我们将测试剪接变异体的假设 包含KCA通道结合子集的特定识别结构域 蛋白质。 4)确定蛋白质磷酸化在调节同一性和 离子通道复合体的功能。我们将检验这一假设 蛋白质磷酸化可以动态重排离子通道的组成 复合体，并因此改变KCA通道的功能 复合体

DESCRIPTION (provided by applicant): A single class of proteins - the ion channels - is the major determinant of neuronal signaling properties, and a long-term objective of this laboratory is to determine the contributions made by individual classes of ion channel to the signaling properties of neurons. Our current focus is on a family of K+ channels, the Ca2+-activated potassium channels because 1) they are found in virtually all neurons and also in many non-neuronal cells, 2) they play numerous functional roles in these various cell types, and 3) the properties of these channels varies in different cellular contexts due to the association of hetero-tetramers, alternative splicing, association with other accessory proteins, and modulation by second messenger cascades. Our specific aims are: 1) Identify and characterize candidate association and tetramerization domains in KCa channels. We will test the hypothesis that KCa channels contain specific protein domains that facilitate the tetramerization of some, and exclusion of other subunits. 2) Identify and characterize intermolecular KCa channel association domains and the resulting protein complexes. We will test the hypothesis that KCa channel a-subunits contain protein domains facilitating the intermolecular binding of other proteins to KCa channel tetramers resulting in novel Kca channel phenotypes. 3) Determine the role of alternative splicing of KCa channel a-subunits on protein complex formation. We will test the hypothesis that splice variants contain specific recognition domains for subsets of Kca channel binding proteins. 4) Determine the role of protein phosphorylation in modulating the identity and functionality of ion channel complexes. We will test the hypothesis that protein phosphorylation can dynamically rearrange the makeup of ion channel complexes, and hence alter the functionality of KCa channels within these complexes