Greer Paul L, Bear Daniel M, Lassance Jean-Marc, Bloom Maria Lissitsyna, Tsukahara Tatsuya, Pashkovski Stan L, Masuda Francis Kei, Nowlan Alexandra C, Kirchner Rory, Hoekstra Hopi E, Datta Sandeep Robert
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Departments of Molecular and Cellular Biology and Organismic and Evolutionary Biology, Center for Brain Science, Harvard University, Howard Hughes Medical Institute, Cambridge, MA 02138, USA.
Cell. 2016 Jun 16;165(7):1734-1748. doi: 10.1016/j.cell.2016.05.001. Epub 2016 May 26.
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.
哺乳动物的气味感知由并行的感觉通路介导，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的七跨膜G蛋白偶联受体（GPCR），这有助于气味辨别。“项链”子系统的感觉神经元位于嗅觉上皮的凹陷处，可检测多种气味剂；然而，它们不表达已知的GPCR气味受体。在这里，我们报告四跨膜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包括信息素和脂肪酸在内的行为学相关配体的反应。单个项链神经元共表达许多MS4A蛋白，并被多种MS4A配体激活；这种信息汇集表明，项链的组织方式更类似于味觉子系统而非嗅觉子系统。因此，MS4A为哺乳动物嗅觉定义了一种独特的机制和功能逻辑。
