Inhibitory signaling in mammalian olfactory transduction potentially mediated by Gα(o).

Inhibitory signaling in mammalian olfactory transduction potentially mediated by Gα(o).
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DOI:
10.1016/j.mcn.2020.103585
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发表时间:
2021-01
影响因子:
3.5
通讯作者:
Ache, Barry W.
Ache, Barry W.
中科院分区:
医学3区
文献类型:
--
作者:
Corey, Elizabeth A.;Ukhanov, Kirill;Bobkov, Yuriy V.;McIntyre, Jeremy C.;Martens, Jeffrey R.;Ache, Barry W.

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哺乳动物嗅觉感受器神经元(ON)中的嗅觉GPCRs(Ors)通过GαS家族成员Gαolf介导兴奋。在这里,我们试探性地将第二个G蛋白Gαo与哺乳动物嗅觉转导中的抑制信号联系起来,首先表明气味引起的依赖于磷脂酰肌醇3-激酶(PI3K)的信号转导抑制在携带有条件的基于OMP-Cre的Gαo基因敲除的小鼠的自然ONON中不存在。然后我们从自然大鼠ONON中鉴定出OR,它们是通过环核苷酸信号被辛醇激活,而被柠檬醛以PI3K依赖的方式抑制的。我们证明了OR激活环核苷酸信号和PI3K信号的方式反映了其在天然OrN中的功能。我们的发现为探索ORs可以与两种不同的G蛋白以一种功能识别的、配体依赖的方式相互作用以介导成熟哺乳动物Orn中的对立信号的有趣可能性奠定了基础。
Olfactory GPCRs (ORs) in mammalian olfactory receptor neurons (ORNs) mediate excitation through the Gαs family member Gαolf. Here we tentatively associate a second G protein, Gαo, with inhibitory signalling in mammalian olfactory transduction by first showing that odor evoked phosphoinositide 3-kinase (PI3K)-dependent inhibition of signal transduction is absent in the native ORNs of mice carrying a conditional OMP-Cre based knockout of Gαo. We then identify an OR from native rat ORNs that are activated by octanol through cyclic nucleotide signaling and inhibited by citral in a PI3K-dependent manner. We show that the OR activates cyclic nucleotide signaling and PI3K signaling in a manner that reflects its functionality in native ORNs. Our findings lay the groundwork to explore the interesting possibility that ORs can interact with two different G proteins in a functionally identified, ligand-dependent manner to mediate opponent signaling in mature mammalian ORNs.
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