Illumination of TAAR2 Location, Function and Regulators

TAAR2 位置、功能和调节器的阐明

基本信息

批准号：
10666759
负责人：
Rong Chen
金额：
$ 15.09万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10666759
关键词：
Address Agonist Amines Animal Model Animals Antibodies Area Biological Models Brain CRISPR/Cas technology Cell membrane Cells Cognition Disorders Confocal Microscopy Corpus striatum structure Cyclic AMP Data Dopamine Dopamine D2 Receptor Drug Regulations Eligibility Determination Endosomes Epitopes Event Family Fluorescent in Situ Hybridization Future G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs GTP-Binding Proteins Genes Golgi Apparatus Homeostasis Human Investigation Ion Channel Knowledge Learning Lighting Location Maps Measures Mediating Mental disorders Midbrain structure Modeling Molecular Mood Disorders Mus Neurobiology Neuroblastoma Pathway interactions Phylogenetic Analysis Physiological Pilot Projects Prefrontal Cortex Protein Kinase Proteins Proteomics Rattus Receptor-Interacting Serine/Threonine Protein Kinase 2 Regulation Research Rewards Rodent Role Signal Transduction Slice Substance Use Disorder System Work cell type dopamine transporter genome editing human disease human model immunocytochemistry interest knockout gene nanomolar nervous system disorder neurotransmission overexpression programs receptor repaired response therapeutic target tool trafficking transmission process

项目摘要

Project Summary This proposal is prepared in response to RFA-RM-22-024, which invites “Pilot projects investigating understudied G protein-coupled receptors, ion channels and protein kinases”. We choose to study trace amine associated receptor 2 (TAAR2) which is an understudied GPCR and an IDG-eligible protein under this FOA. TAAR2 was discovered as a GPCR in 2001 and has been speculated to be involved in neurological and psychiatric diseases; however, little progress has been made towards understanding the action of TAAR2 and creating experimental tools. To address the current knowledge gap, we will investigate TAAR2 cellular and subcellular localization, trafficking and signal transduction using human SH-SY5Y cells and rodent brains. Further, this proposal will also apply CRISPR/Cas9-mediated homology-directed repair mechanism to tag Taar2 gene in SH-SY5Y cells so that TAAR2-interacting protein network can be revealed through proteomics. Knowledge learned and products generated from this proposal will add value to the IDG program and importantly, lay ground work for future investigation of TAAR2 in animal models of human diseases.

项目概要该提案是为了响应 RFA-RM-22-024 而准备的，该提案邀请“试点项目调查 “未充分研究的G蛋白偶联受体、离子通道和蛋白激酶”我们选择研究微量胺。相关受体 2 (TAAR2) 是一种正在研究的 GPCR，也是该 FOA 下的 IDG 合格蛋白。 TAAR2 于 2001 年作为 GPCR 被发现，推测与神经系统和然而，对于 TAAR2 和精神疾病的作用的理解进展甚微。为了解决当前的知识差距，我们将研究 TAAR2 细胞和使用人类 SH-SY5Y 细胞和啮齿动物大脑进行亚细胞定位、运输和信号转导。此外，该提案还将应用CRISPR/Cas9介导的同源定向修复机制来标记 SH-SY5Y细胞中的Taar2基因，以便通过蛋白质组学揭示TAAR2相互作用的蛋白网络。从该提案中学到的知识和产生的产品将为 IDG 计划增加价值，重要的是，为未来在人类疾病动物模型中研究 TAAR2 奠定基础。