Abe Takayuki, Touhara Kazushige
*Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
Biochem Soc Trans. 2014 Aug;42(4):873-7. doi: 10.1042/BST20140051.
Mammals use pheromones to communicate with other animals of the same species. In mice, the VNO (vomeronasal organ) has a pivotal role in pheromone detection. We discovered a 7 kDa peptide, ESP1 (exocrine-gland-secreting peptide 1), in tear fluids from male mice that enhances the sexual behaviour of female mice via the VNO. NMR studies demonstrate that ESP1 adopts a compact structure with a helical fold stabilized by an intramolecular disulfide bridge. Functional analysis in combination with docking simulation indicates that ESP1 is recognized by a specific G-protein-coupled vomeronasal receptor, V2Rp5, via charge-charge interactions in the large extracellular region of the receptor. ESP1 is a member of the ESP family, which comprises 38 homologous genes in mice, and some of these genes are expressed in a sex- or age-dependent manner. Most recently, ESP22 was found to be released specifically in juvenile tear fluids and to inhibit the sexual behaviour of adult male mice. These studies demonstrate that peptide pheromones are used for chemical communication in mice, and they indicate a structural basis for the narrowly tuned perception of mammalian peptide pheromones by vomeronasal receptors.
哺乳动物利用信息素与同物种的其他动物进行交流。在小鼠中，犁鼻器（VNO）在信息素检测中起关键作用。我们在雄性小鼠的泪液中发现了一种7 kDa的肽，即外分泌腺分泌肽1（ESP1），它通过犁鼻器增强雌性小鼠的性行为。核磁共振研究表明，ESP1具有紧密的结构，其螺旋折叠由分子内二硫键稳定。结合对接模拟的功能分析表明，ESP1通过与受体大细胞外区域的电荷-电荷相互作用，被一种特定的G蛋白偶联犁鼻器受体V2Rp5识别。ESP1是ESP家族的成员，该家族在小鼠中包含38个同源基因，其中一些基因以性别或年龄依赖的方式表达。最近发现，ESP22专门在幼年小鼠的泪液中释放，并抑制成年雄性小鼠的性行为。这些研究表明，肽类信息素用于小鼠的化学通讯，并且它们揭示了犁鼻器受体对哺乳动物肽类信息素进行精细调节感知的结构基础。
