Low signaling efficiency from receptor to effector in olfactory transduction: A quantified ligand-triggered GPCR pathway.
Low signaling efficiency from receptor to effector in olfactory transduction: A quantified ligand-triggered GPCR pathway.
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DOI：
10.1073/pnas.2121225119
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发表时间：
2022-08-09
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
作者：
G蛋白偶联受体（GPCR）信号是细胞中最常见的信号基序。基本途径由一个GPCR分子组成，一旦受到刺激，就会继续激活G蛋白，而G蛋白又会激活效应酶来产生细胞功能。关于GPCR信号传导的一个长期存在的概念是高扩增，这个概念起源于对杆状光转导的研究，后来变成了教科书式的教条；即一个GPCR分子激活大量下游G蛋白分子。我们在哺乳动物嗅觉转导方面的发现现在表明，即使对于一个匹配良好的气味/受体复合物，这种放大也不是统一的。因此，杆光转导可能是不寻常的，并不一定代表配体触发的GPCR信号。G蛋白偶联受体（GPCR）信号是普遍存在的。作为该信号基元的原型，杆光转导提供了许多基本的定量细节，包括一个活性GPCR分子激活大量下游G蛋白/酶效应复合物的规律。然而，杆光导是光激活的，而GPCR途径主要是配体激活的。在这里，我们报告了哺乳动物嗅觉转导中配体触发的GPCR途径的详细研究，发现一个气味受体分子（一次性）与其最有效的气味剂络合时平均产生的下游效应物要少得多。进一步的实验给出了暂定的成功概率为~ 10−4（更保守的是~ 10−2到~ 10−5）。这幅图可能比杆状光转导更能代表GPCR信号，构成了一种范式转变。
G protein–coupled receptor (GPCR) signaling is the most prevalent signaling motif in cells. The basic pathway consists of a GPCR molecule that, once stimulated, goes on to activate a G protein, which in turn typically activates an effector enzyme to produce a cellular function. One long-standing concept about GPCR signaling, originating from a study in rod phototransduction turned into textbook dogma, is high amplification; namely, a large number of downstream G protein molecules are activated by one GPCR molecule. Our findings here from mammalian olfactory transduction now indicate that this amplification is less than unity even for a well-matched odorant/receptor complex. Thus, rod phototransduction is possibly unusual and not necessarily representative of ligand-triggered GPCR signaling generally. G protein–coupled receptor (GPCR) signaling is ubiquitous. As an archetype of this signaling motif, rod phototransduction has provided many fundamental, quantitative details, including a dogma that one active GPCR molecule activates a substantial number of downstream G protein/enzyme effector complexes. However, rod phototransduction is light-activated, whereas GPCR pathways are predominantly ligand-activated. Here, we report a detailed study of the ligand-triggered GPCR pathway in mammalian olfactory transduction, finding that an odorant-receptor molecule when (one-time) complexed with its most effective odorants produces on average much less than one downstream effector. Further experiments gave a nominal success probability of tentatively ∼10−4 (more conservatively, ∼10−2 to ∼10−5). This picture is potentially more generally representative of GPCR signaling than is rod phototransduction, constituting a paradigm shift.
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影响因子：
3.7
作者：
Bubnell J;Jamet S;Tomoiaga D;D'Hulst C;Krampis K;Feinstein P
通讯作者：
Feinstein P
DOI：
10.1073/pnas.1004571107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Bhandawat, Vikas;Reisert, Johannes;Yau, King-Wai
通讯作者：
Yau, King-Wai
DOI：
10.1002/neu.480280109
发表时间：
1995-09-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHERRY, JA;DAVIS, RL
通讯作者：
DAVIS, RL
影响因子：
56.9
作者：
JONES, DT;REED, RR
通讯作者：
REED, RR
DOI：
10.1085/jgp.201110645
发表时间：
2011-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Reisert J;Zhao H
通讯作者：
Zhao H