The Neuronal alpha-bungarotoxin Binding Site

神经元nAChRs由许多亚型组成，根据它们的不同而分类 中枢神经系统和外周神经系统的药理和分布。我们 建议研究一个这样的亚型，神经性a-银环蛇毒素结合受体(Bgtr)。 在这份拨款申请中。与其他离子亲和性相比，bgtr是不寻常的。 神经递质受体，因为它们由单一的亚单位亚型7 亚单位。此外，在大多数细胞中，？7亚基不能折叠和组装成Bgtr。 只有在正确的细胞环境中才能形成Bgtr，主要是在神经元中。因此，？7个亚基 需要一个或多个神经元特有的处理事件或神经元特有的蛋白质 命令组装成Bgtr。我们研究的总体目标一直是确定和 表征BgtR中涉及的神经元特异性处理事件和蛋白质 表情。在之前的资助期间，我们能够识别蛋白质 棕榈酰化是BgtR所需的神经元特异性翻译后修饰 表情。我们还一直在研究一种神经元蛋白，Ric-3，它也有助于 介导BgtR的表达。这项提案的主要目标是描述 BgtR亚基棕榈酰化和Ric-3在调节BgtR表达中的作用 异源表达或在神经元中表达。具体来说，我们将标识 棕榈酰化7亚基的机械，测试7的附加后果 亚基棕榈酰化、Ric-3决定区介导其对BgtRs和BgtRs的影响 研究Ric-3如何改变翻译后加工？7个亚基。离子神经递质受体对于突触传递是必不可少的，并且 负责神经和肌肉对神经递质的快速反应。在这 建议，我们将研究一种特定神经元尼古丁的表达调控 乙酰胆碱受体(NAChR)亚型，银环蛇毒素结合受体(BgtR)， 这是一种离子神经递质受体。作为尼古丁结合的部位 大脑，这些受体负责尼古丁成瘾，并在 神经退行性疾病和精神疾病，如阿尔茨海默病和 精神分裂症。

Neuronal nAChRs are composed of a number of subtypes as classified by their diverse pharmacology and distribution in the central and peripheral nervous system. We propose to study one such subtype, the neuronal a-bungarotoxin binding receptor (BgtR) in this grant application. BgtRs are unusual compared to other ionotropic neurotransmitter receptors in that they composed of single subunit subtype, the ¿7 subunit. Additionally, ¿7 subunits fail to fold and assemble into BgtRs in most cells and only form BgtRs in the correct cellular environment, mainly in neurons. Thus, ¿7 subunits require one or more neuronal-specific processing events or neuronal-specific proteins in order to assemble into BgtRs. The overall goal of our research has been to identify and characterize the neuronal-specific processing events and proteins involved in BgtR expression. In the previous funding period, we were able to identify protein palmitoylation as a neuronal-specific posttranslational modification required for BgtR expression. We also have been characterizing a neuronal protein, Ric-3, that also helps mediate BgtR expression. The main objective of this proposal is to characterize the roles of subunit palmitoylation and Ric-3 in regulating BgtR expression when BgtRs are expressed heterologously or in neurons. Specifically, we will be identifying the machinery that palmitoylates ¿7 subunits, testing for additional consequences of ¿7 subunit palmitoylation, determining region of Ric-3 mediating its effects on BgtRs and examining how Ric-3 alters the posttranslational processing ¿7 subunits. Ionotropic neurotransmitter receptors are essential for synaptic transmission and are responsible for the rapid responses to neurotransmitters in nerve and muscle. In this proposal, we will study the regulation of the expression of a specific neuronal nicotinic acetylcholine receptor (nAChR) subtype, the ¿-bungarotoxin binding receptor (BgtR), which is an ionotropic neurotransmitter receptor. As the site where nicotine binds in the brain, these receptors are responsible for nicotine addiction and also play a role in neurodegenerative and psychiatric diseases such as Alzheimers disease and schizophrenia.