Identification of protein pheromones that promote aggressive behaviour
Identification of protein pheromones that promote aggressive behaviour
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DOI：
10.1038/nature05997
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发表时间：
2007-12-06
期刊：
影响因子：
64.8
通讯作者：
Stowers, Lisa
中科院分区：
文献类型：
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作者：
Chamero, Pablo;Marton, Tobias F.;Stowers, Lisa
老鼠使用信息素，由同一物种的成员发出和检测的化合物，作为调节社会行为的线索，如幼崽哺乳，攻击和交配（1）。检测信息素的神经元被认为存在于鼻腔内至少两个独立的器官中：犁鼻器（VNO）和主嗅上皮（莫伊）（2）。每个信息素配体被认为激活这些感觉神经元的专用子集。然而，信息素线索的性质和调节特定社会行为的响应神经元的身份在很大程度上是未知的。在这里，我们表明，通过直接激活的感觉神经元和分析的行为，至少有两个化学上不同的配体足以促进男性的侵略和刺激VNO神经元。我们已经纯化并分析了其中一类配体，并发现其特异性的攻击促进活性取决于主要尿蛋白（MUP）复合物的蛋白组分的存在，已知该复合物包含与小有机分子结合的专门的脂质运载蛋白（1，3，4）。利用分离的犁鼻神经元（VN）的钙成像，我们已经确定MUP蛋白激活感觉神经元亚家族，其特征在于G蛋白G α（o）亚基（也称为Gnao）和Vmn 2 r推定信息素受体（V2 Rs）的表达。基因组分析表明，种特异性的MUP和V2 Rs的共扩增，如将预期之间的信息素信号组件。最后，我们表明，由MUPs引起的攻击行为发生完全通过VNO神经元回路。我们的研究结果证实了MUP蛋白作为信息素配体通过辅助嗅觉神经通路介导雄性-雄性攻击的想法。
Mice use pheromones, compounds emitted and detected by members of the same species, as cues to regulate social behaviours such as pup suckling, aggression and mating(1). Neurons that detect pheromones are thought to reside in at least two separate organs within the nasal cavity: the vomeronasal organ (VNO) and the main olfactory epithelium (MOE)(2). Each pheromone ligand is thought to activate a dedicated subset of these sensory neurons. However, the nature of the pheromone cues and the identity of the responding neurons that regulate specific social behaviours are largely unknown. Here we show, by direct activation of sensory neurons and analysis of behaviour, that at least two chemically distinct ligands are sufficient to promote male-male aggression and stimulate VNO neurons. We have purified and analysed one of these classes of ligand and found its specific aggression-promoting activity to be dependent on the presence of the protein component of the major urinary protein (MUP) complex, which is known to comprise specialized lipocalin proteins bound to small organic molecules(1,3,4). Using calcium imaging of dissociated vomeronasal neurons (VNs), we have determined that the MUP protein activates a sensory neuron subfamily characterized by the expression of the G-protein G alpha(o) subunit ( also known as Gnao) and Vmn2r putative pheromone receptors (V2Rs). Genomic analysis indicates species-specific co-expansions of MUPs and V2Rs, as would be expected among pheromone-signalling components. Finally, we show that the aggressive behaviour induced by the MUPs occurs exclusively through VNO neuronal circuits. Our results substantiate the idea of MUP proteins as pheromone ligands that mediate male-male aggression through the accessory olfactory neural pathway.