Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Department of Animal Physiology, Institute of Biology/Zoology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
EMBO J. 2018 Jan 4;37(1):39-49. doi: 10.15252/embj.201797155. Epub 2017 Sep 28.
Many animals respond to threats by releasing alarm pheromones (APs) that warn conspecifics. In mice, detection of the AP 2-sec-butyl-4,5-dihydrothiazole (SBT) is mediated by chemosensory neurons residing in the Grueneberg ganglion (GG) of the anterior nasal region. Although the molecular mechanisms underlying activation of GG neurons by SBT and other substances are still unclear, recent studies have reported an involvement of the transmembrane guanylyl cyclase (GC) subtype GC-G in chemosensory signaling in the GG Here, we show that SBT directly binds with high affinity to the extracellular domain of GC-G and elicits an enhanced enzymatic activity of this protein. In line with this finding, heterologous expression of GC-G renders cells responsive to SBT while activation by SBT was strongly attenuated in GG neurons from GC-G-deficient mice. Consistently, SBT-induced fear-associated behaviors, SBT-evoked elevated blood pressure, and increased serum levels of the stress hormone corticosterone were clearly reduced in GC-G-knockout animals compared to wild-type mice. These observations suggest that GC-G serves as an unusual receptor in GG neurons mediating the detection of the volatile AP substance SBT.
许多动物通过释放报警信息素来对威胁做出反应，这些信息素可以警告同种生物。在老鼠中，对 2-丁基-4,5-二氢噻唑（SBT）的检测是由位于前鼻区的 Grüneberg 神经节（GG）中的化学感觉神经元介导的。尽管 SBT 和其他物质激活 GG 神经元的分子机制尚不清楚，但最近的研究报告称，跨膜鸟苷酸环化酶（GC）亚型 GC-G 参与 GG 中的化学感觉信号传递。在这里，我们表明 SBT 与 GC-G 的细胞外结构域具有高亲和力结合，并引发该蛋白的酶活性增强。与这一发现一致的是，GC-G 的异源表达使细胞对 SBT 产生反应，而 GC-G 缺陷小鼠 GG 神经元中的 SBT 激活则被强烈减弱。一致地，与野生型小鼠相比，GC-G 基因敲除动物中 SBT 诱导的恐惧相关行为、SBT 引起的血压升高以及应激激素皮质酮的血清水平明显降低。这些观察结果表明，GC-G 作为 GG 神经元中的一种不寻常受体，介导对挥发性报警信息素 SBT 的检测。
