A Family of non-GPCR Chemosensors Defines an Alternative Logic for Mammalian Olfaction.
A Family of non-GPCR Chemosensors Defines an Alternative Logic for Mammalian Olfaction.
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DOI：
10.1016/j.cell.2016.05.001
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发表时间：
2016-06-16
期刊：
影响因子：
64.5
通讯作者：
Datta SR
中科院分区：
文献类型：
--
作者：
Greer PL;Bear DM;Lassance JM;Bloom ML;Tsukahara T;Pashkovski SL;Masuda FK;Nowlan AC;Kirchner R;Hoekstra HE;Datta SR
哺乳动物的气味感知是由平行的感觉通路介导的，这些通路传递有关嗅觉世界的不同信息。多个嗅觉子系统以每个神经元一个受体的模式表达特征性七跨膜 G 蛋白偶联受体 (GPCR)，从而促进气味辨别。 “项链”子系统的感觉神经元位于嗅觉上皮的隐窝内，可以检测不同的气味；然而，它们不表达已知的 GPCR 气味受体。在这里，我们报道四次跨膜 MS4A 蛋白家族的成员是在项链感觉神经元内表达的化学传感器。这些受体定位于感觉末梢，并在体外和体内赋予对行为学相关配体（包括信息素和脂肪酸）的反应。单个项链神经元共表达许多 MS4A 蛋白，并被多个 MS4A 配体激活；这种信息汇集表明，项链的组织方式更像是味觉子系统，而不是嗅觉子系统。因此，MS4A 定义了哺乳动物嗅觉的独特机制和功能逻辑。
Odor perception in mammals is mediated by parallel sensory pathways that convey distinct information about the olfactory world. Multiple olfactory subsystems express characteristic seven-transmembrane G-protein coupled receptors (GPCRs) in a one-receptor-per-neuron pattern that facilitates odor discrimination. Sensory neurons of the “necklace” subsystem are nestled within the recesses of the olfactory epithelium and detect diverse odorants; however, they do not express known GPCR odor receptors. Here we report that members of the four-pass transmembrane MS4A protein family are chemosensors expressed within necklace sensory neurons. These receptors localize to sensory endings and confer responses to ethologically-relevant ligands including pheromones and fatty acids in vitro and in vivo. Individual necklace neurons co-express many MS4A proteins and are activated by multiple MS4A ligands; this pooling of information suggests that the necklace is organized more like subsystems for taste than for smell. The MS4As therefore define a distinct mechanism and functional logic for mammalian olfaction.