Calcium Activated K+ Channels in Brain

描述（由申请人提供）：一类蛋白质-离子 通道-是神经元信号传导特性的主要决定因素， 该实验室的长期目标是确定 通过个别种类的离子通道来调节神经元的信号传导特性。 我们目前的重点是一个家庭的K+通道，钙激活钾 通道，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。 非神经元细胞，2）它们在这些不同的功能中发挥着许多作用 细胞类型，以及3）这些通道的性质在不同的细胞中不同， 由于异源四聚体的缔合， 剪接，与其他辅助蛋白的结合，以及第二次 信使级联。我们的具体目标是： 1)鉴定和表征候选缔合和四聚化结构域 KCa频道我们将检验KCa通道含有特定的 蛋白质结构域，促进四聚体的一些，并排除 其他子单位。 2)鉴定和表征分子间KCa通道缔合结构域， 产生的蛋白质复合物。我们将检验KCa通道 α-亚基含有促进以下物质分子间结合的蛋白质结构域： 其他蛋白质与KCa通道四聚体结合，产生新的KCa通道 表型 3)确定KCa通道α-亚基的选择性剪接对 蛋白质复合物形成。我们将检验剪接变异体 含有Kca通道结合亚组的特异性识别结构域 proteins. 4)确定蛋白质磷酸化在调节身份中的作用， 离子通道复合物的功能。我们将检验这个假设， 蛋白质磷酸化可以动态地重排离子通道的组成 复合物，从而改变这些KCa通道的功能， 配合物

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