Role of the scaffolding protein SLC9A3R1 in the vomeronasal organ - from protein interactions to the physiology of pheromone detection

支架蛋白 SLC9A3R1 在犁鼻器中的作用 - 从蛋白质相互作用到信息素检测的生理学

• 批准号: 220234083
• 负责人: Professorin Dr. Eva Maria Neuhaus
• 金额: --
• 依托单位: Arbeitsgruppe Chemosensorik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/220234083?language=en
• 关键词: Role; scaffolding; protein; SLC9A3R1; vomeronasal

In most mammals, the vomeronasal system detects of a variety of (semio)chemicals that mediate olfactory-driven social and sexual behaviors. Vomeronasal chemosensation depends on G protein-coupled receptors (V1R, V2R, FPR-rs) that operate at remarkably low stimulus concentrations, thus, indicating a highly sensitive and efficient signaling pathway. We therefore hypothesize a) that vomeronasal signaling cascade proteins are organized in microdomains to ensure optimal signal transduction, and b) that the assembly of these domains involves scaffolding proteins. In the present proposal, we aim to identify and investigate PDZ domain-containing proteins as putative molecular organizers of signal transduction in vomeronasal neurons. Accordingly, a major goal of this research is to analyze the functional role of scaffolding proteins in shaping ultrasensitive and highly selective pheromone responses. SLC9A3R1, a protein that contains two PDZ domains and a carboxy-terminal ezrin-binding domain, is the focus of our interest. We will identify the molecular composition of vomeronasal SLC9A3R1-based scaffolds, study distribution of SLC9A3R1, associated receptor proteins and downstream signaling partners at high resolution, and employ an array of physiological approaches to elucidate the function of protein - protein interactions in vomeronasal signaling.

在大多数哺乳动物中，犁鼻系统检测到各种（半）化学物质，介导嗅觉驱动的社会和性行为。犁鼻化学感觉依赖于G蛋白偶联受体（V1 R，V2 R，FPR-rs），在非常低的刺激浓度下工作，因此，表明一个高度敏感和有效的信号通路。因此，我们假设a）犁鼻信号级联蛋白被组织在微结构域中以确保最佳的信号转导，和B）这些结构域的组装涉及支架蛋白。在目前的建议中，我们的目标是确定和调查PDZ结构域的蛋白质作为犁鼻神经元信号转导的假定分子组织者。因此，本研究的一个主要目标是分析支架蛋白在塑造超敏感和高选择性信息素反应中的功能作用。SLC 9A 3R 1是一个含有两个PDZ结构域和一个羧基端ezrin结合结构域的蛋白质，是我们感兴趣的焦点。我们将确定犁鼻SLC 9A 3R 1为基础的支架的分子组成，研究分布的SLC 9A 3R 1，相关的受体蛋白和下游信号合作伙伴在高分辨率，并采用一系列的生理方法来阐明蛋白质-蛋白质相互作用的功能犁鼻信号。

项目成果

Elevated Cytosolic Cl- Concentrations in Dendritic Knobs of Mouse Vomeronasal Sensory Neurons.

小鼠犁鼻感觉神经元树突状突起中胞质 Cl 浓度升高

• DOI: 10.1093/chemse/bjw077
• 发表时间: 2016
• 期刊: Chemical senses
• 影响因子: 3.5
• 作者: Untiet V;Moeller LM;Ibarra-Soria X;Sánchez-Andrade G;Stricker M;Neuhaus EM;Logan DW;Gensch T;Spehr M
• 通讯作者: Spehr M

The scaffold protein MUPP1 regulates odorant-mediated signaling in olfactory sensory neurons

支架蛋白 MUPP1 调节嗅觉感觉神经元中气味介导的信号传导

• DOI: 10.1242/jcs.144220
• 发表时间: 2014
• 期刊: Journal of Cell Science
• 影响因子: 4
• 作者: Baumgart S;Jansen F;Bintig W;Kalbe B;Herrmann C;Klumpers F;Köster SD;Scholz P;Rasche S;Dooley R;Metzler-Nolte N;Spehr M;Hatt H;Neuhaus EM
• 通讯作者: Neuhaus EM