Medical Faculty, Rudolf Schönheimer Institute of Biochemistry, Leipzig University, 04103 Leipzig, Germany.
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
G3 (Bethesda). 2024 Nov 6;14(11). doi: 10.1093/g3journal/jkae206.
Adhesion G protein-coupled receptors are unique molecules. They are able to transmit classical signals via G protein activation as well as mediate functions solely through their extracellular N termini, completely independently of the seven transmembrane helices domain and the C terminus. This dual mode of action is highly unusual for G protein-coupled receptors and allows for a plethora of possible cellular consequences. However, the physiological implications and molecular details of this N terminus-mediated signaling are poorly understood. Here, we show that several distinct seven transmembrane helices domain-independent/trans functions of the adhesion G protein-coupled receptor latrophilin homolog latrophilin-1 in the nematode Caenorhabditis elegans together regulate reproduction: sperm guidance, ovulation, and germ cell apoptosis. In these contexts, the receptor elicits its functions in a noncell autonomous manner. The functions might be realized through alternative splicing of the receptor specifically generating N terminus-only variants. Thus, our findings shed light on the versatility of seven transmembrane helices domain-independent/N terminus-only/trans functions of adhesion G protein-coupled receptor and discuss possible molecular details.
黏附 G 蛋白偶联受体是独特的分子。它们能够通过 G 蛋白激活传递经典信号，也能够仅通过其细胞外 N 末端介导功能，完全独立于七个跨膜螺旋域和 C 末端。这种双重作用模式对于 G 蛋白偶联受体来说非常不寻常，允许产生大量可能的细胞后果。然而，这种 N 末端介导的信号转导的生理意义和分子细节还知之甚少。在这里，我们表明，线虫秀丽隐杆线虫中黏附 G 蛋白偶联受体 latrophilin 同源物 latrophilin-1 的几个不同的七跨膜螺旋域非依赖性/跨膜功能共同调节生殖：精子导向、排卵和生殖细胞凋亡。在这些情况下，该受体以非细胞自主的方式发挥其功能。这些功能可能是通过受体的选择性剪接特异性产生仅 N 末端变体来实现的。因此，我们的发现揭示了黏附 G 蛋白偶联受体的七跨膜螺旋域非依赖性/N 末端仅/跨膜功能的多功能性，并讨论了可能的分子细节。
