iRhom2在嗅觉中的作用:对气味受体调节和活动依赖的适应的影响
Stephanie A Azzopardi1,2,3, Hsiu-Yi Lu4, Sebastien Monette5
1Weill Cornell Medicine/Rockefeller University/Memorial Sloan-Kettering Cancer Center, Tri-Institutional MD-PhD Program, New York, NY 10021, USA.
International journal of molecular sciences
|June 19, 2024
概括
iRhom2在嗅觉感官神经元 (OSN) 中独特表达,并调节嗅觉受体 (OR) 基因表达. 气味刺激激活iRhom2/ADAM17,影响ORs并创建一个反循环来降低iRhom2.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- ADAM17和iRhoms通过释放膜蛋白来调节细胞与细胞之间的相互作用.
- iRhom2通常在髓状细胞中发现,而iRhom1在小鼠大脑中占主导地位.
- 嗅觉感官神经元 (OSNs) 表达了大量的嗅觉受体 (ORs).
研究的目的:
- 研究iRhom2在嗅觉感官神经元 (OSN) 中的独特作用.
- 为了确定嗅觉受体 (OR) 是否可以激活iRhom2/ADAM17通路.
- 阐明将气味刺激与OSN下游转录变化的机制.
主要方法:
- 对iRhom2-/-小鼠的嗅觉感官神经元 (OSN) 中iRhom2表达的分析.
- RNA测序 (RNAseq) 来评估嗅觉受体 (OR) 基因表达.
- 通过嗅觉受体 (OR2AT4) 激动剂对iRhom2/ADAM17通路激活的研究.
主要成果:
- iRhom2在OSNs中唯一表达;iRhom2-/-小鼠显示ORs子集的改变表达.
- 在iRhom2-/-小鼠中表达某些OR的OSN在暴露于气味时表现出减少的基因表达变化.
- 气味暴露会负面调节iRhom2表达,OR激活可以触发iRhom2/ADAM17依赖的信号.
结论:
- 气味刺激激活OSN中的iRhom2/ADAM17,导致OR和活性基因的转录性变化.
- 这个过程建立了一个负反循环,降低iRhom2表达的调节.
- iRhom2在调节嗅觉受体谱和对气味刺激的反应方面发挥着至关重要的作用.
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