Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, 04103, Leipzig, Germany.
Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, Leipzig University, 04103, Leipzig, Germany; Institute of Cell Biology, Department of Biology, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
Biochem Biophys Res Commun. 2022 Jan 22;589:152-158. doi: 10.1016/j.bbrc.2021.12.006. Epub 2021 Dec 5.
Latrophilins are highly conserved Adhesion GPCRs playing essential roles in the mammalian nervous system and are associated with severe neurological disorders. Recently, it has been shown that murine Latrophilins mediate classical G-protein signals to drive synaptogenesis. However, there is evidence that Latrophilins in the nematode Caenorhabditis elegans can also function independently of their seven-transmembrane domain and C terminus (trans function). Here, we show that Latrophilin-1 acts in trans to mediate morphogenesis of sensory structures in the C. elegans nervous system. This trans function is physiologically relevant in copulation behavior. Detailed expression and RNA-Seq analyses revealed specific LAT-1-positive neurons and first insights into the genetic network that is modulated by the receptor function. We conclude that 7TM-independent functions of Latrophilins are essential for neuronal physiology, possibly complementing canonical functions via G protein-mediated signaling.
拉托菲尔蛋白是高度保守的粘附 GPCR，在哺乳动物神经系统中发挥重要作用，并与严重的神经紊乱有关。最近的研究表明，鼠类拉托菲尔蛋白介导经典 G 蛋白信号以驱动突触发生。然而，有证据表明，线虫秀丽隐杆线虫中的拉托菲尔蛋白也可以独立于其七跨膜域和 C 末端（跨功能）发挥作用。在这里，我们表明拉托菲尔蛋白-1 以转位方式介导秀丽隐杆线虫神经系统中感觉结构的形态发生。这种转位功能在交配行为中具有生理相关性。详细的表达和 RNA-Seq 分析揭示了特定的 LAT-1 阳性神经元，并首次深入了解了受受体功能调节的遗传网络。我们得出结论，拉托菲尔蛋白的 7TM 非依赖性功能对神经元生理学至关重要，可能通过 G 蛋白介导的信号传递来补充经典功能。
