Biogenesis of olfactory G protein-coupled receptors

嗅觉 G 蛋白偶联受体的生物发生

• 批准号: 10200752
• 负责人: Hiroaki Matsunami
• 金额: $ 43.89万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200752
• 关键词: Affect; Amino Acids; Animals; Area; Axon; Biogenesis; Biological Assay; Cardiac; Carrier Proteins; Cell Lineage; Cell Surface Receptors; Cell membrane; Cell surface; Cells; Complex; Coupled; Development; Disease; Endoplasmic Reticulum; Exhibits; Family; Fluorescence-Activated Cell Sorting; G-Protein-Coupled Receptors; GTP-Binding Proteins; Gene Expression Regulation; Genetic; Goals; In Situ Hybridization; Individual; Integral Membrane Protein; Knock-in Mouse; Knockout Mice; Knowledge; Label; Light; Link; Malignant Neoplasms; Mammals; Mediating; Molecular; Mus; Mutation Analysis; Neurologic; Odorant Receptors; Odors; Olfactory Receptor Cells; Organ; Outcome; Peripheral; Pharmacologic Substance; Physiology; Play; Process; Proteins; Receptor Gene; Regulation; Research; Role; Smell Perception; Specific qualifier value; Structure; Testing; Transcriptional Regulation; Transmembrane Domain; base; experimental study; gene function; in vivo; in vivo evaluation; knockout gene; mouse model; mutant; novel; olfactory bulb glomeruli; olfactory receptor; olfactory sensory neurons; protein expression; protein transport; receptor; receptor expression; response; simulation; trafficking; transcriptome; transcriptome sequencing

Biogenesis of G protein-coupled receptors (GPCRs), the largest molecular class of pharmaceutical targets for cardiac, psychiatric, and cancer diseases is a complex and underexplored process. Many GPCRs require the presence of specific accessory proteins or co-receptors for their cell surface trafficking and/or functional expression. We previously identified RTP1 (Receptor Transporting Protein 1) and RTP2, both of which are single transmembrane proteins strongly and exclusively expressed in the peripheral olfactory organs. They greatly enhance trafficking of olfactory receptors (ORs) on the cell surface and induce functional expression in heterologous cells. In preliminary studies we investigated the roles played by the RTPs in vivo using the RTP1 and RTP2 double gene knockout mice (RTP1,2(-/-)), and uncovered an unexpected link between OR trafficking and OR gene choice mediated by the RTPs. Based on these and other preliminary studies, we will test three hypotheses. These are 1) RTP1 and RTP2 influence OR gene choice, 2) RTP mutant animals use diminished repertoire of functional ORs, and 3) specific residues of ORs regulate ER retention and cell surface trafficking. The successful completion of the project will deepen our understanding of OR biogenesis and function, and sheds light on the new link between OR protein trafficking and OR transcriptional regulation.

G蛋白偶联受体（gpcr）是生物发生学中最大的分子类药物靶标

项目成果

Sex steroid hormone synthesis, metabolism, and the effects on the mammalian olfactory system.

• DOI: 10.1007/s00441-022-03707-9
• 发表时间: 2023-01
• 期刊: Cell and tissue research
• 影响因子: 3.6

Real-time In Vitro Monitoring of Odorant Receptor Activation by an Odorant in the Vapor Phase

• DOI: 10.3791/59446
• 发表时间: 2019-04-01
• 期刊: JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
• 影响因子: 1.2
• 作者: de March, Claire A.;Fukutani, Yosuke;Matsunami, Hiroaki
• 通讯作者: Matsunami, Hiroaki

Axonal Odorant Receptors Mediate Axon Targeting

轴突气味受体介导轴突靶向

• DOI: 10.1016/j.celrep.2019.11.099
• 发表时间: 2019
• 期刊: Cell Reports
• 影响因子: 8.8
• 作者: Zamparo Ilaria;Francia Simona;Franchi Sira Angela;Redolfi Nelly;Costanzi Elisa;Kerstens Axelle;Fukutani Yosuke;Battistutta Roberto;Polverino de Laureto Patrizia;Munck Sebastian;De Strooper Bart;Matsunami Hiroaki;Lodovichi Claudia
• 通讯作者: Lodovichi Claudia

Concentration-Dependent Recruitment of Mammalian Odorant Receptors.

哺乳动物气味受体的浓度依赖性招募。

• DOI: 10.1523/eneuro.0103-19.2019
• 发表时间: 2020
• 期刊: eNeuro
• 影响因子: 3.4
• 作者: Hu,XiaoyangSerene;Ikegami,Kentaro;Vihani,Aashutosh;Zhu,KevinW;Zapata,Marcelo;deMarch,ClaireA;Do,Matthew;Vaidya,Natasha;Kucera,Gary;Bock,Cheryl;Jiang,Yue;Yohda,Masafumi;Matsunami,Hiroaki
• 通讯作者: Matsunami,Hiroaki

Generation and Characterization of a Cell Type-Specific, Inducible Cre-Driver Line to Study Olfactory Processing.

• DOI: 10.1523/jneurosci.3076-20.2021
• 发表时间: 2021-07-28
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Koldaeva A;Zhang C;Huang YP;Reinert JK;Mizuno S;Sugiyama F;Takahashi S;Soliman T;Matsunami H;Fukunaga I
• 通讯作者: Fukunaga I