Daniel Matúš, Willem Berend Post, Victoria Elisabeth Groß, Alexander Bernd Knierim, Christina Katharina Kuhn, Franziska Fiedler, Darian Benno Tietgen, Johanna Lena Schön, Torsten Schöneberg, Simone Prömel
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引用次数: 0
摘要
粘附 G 蛋白偶联受体(aGPCR)是一种独特的分子。它们既能通过 G 蛋白激活传递经典信号,又能完全独立于七膜螺旋结构域(7TM)和 C 末端,仅通过细胞外 N 末端介导功能。这种双重作用模式在 GPCR 中极为罕见,并可能对细胞产生多种影响。然而,人们对这种由 N 端介导的信号转导的生理意义和分子细节知之甚少。在这里,我们发现在线虫秀丽隐杆线虫中,aGPCR Latrophilin 同源物 LAT-1 的几种不同的 7TM 独立/反式功能共同调节着生殖:精子引导、排卵和生殖细胞凋亡。在这些情况下,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替代剪接实现的,这种剪接特异性地产生了仅有 N 末端的变体。因此,我们的研究结果揭示了 aGPCR 的 7TM 独立/仅 N 末端/反式功能的多样性,并讨论了可能的分子细节。
The N terminus-only (trans) function of the Adhesion GPCR Latrophilin-1 controls multiple processes in reproduction of C. elegans.
Adhesion G protein-coupled receptors (aGPCR) 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 (7TM) and the C terminus. This dual mode of action is highly unusual for GPCRs 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 7TM-independent/trans functions of the aGPCR Latrophilin homolog LAT-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 non-cell 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 7TM-independent/N terminus-only/trans functions of aGPCR and discuss possible molecular details.
期刊介绍:
G3: Genes, Genomes, Genetics provides a forum for the publication of high‐quality foundational research, particularly research that generates useful genetic and genomic information such as genome maps, single gene studies, genome‐wide association and QTL studies, as well as genome reports, mutant screens, and advances in methods and technology. The Editorial Board of G3 believes that rapid dissemination of these data is the necessary foundation for analysis that leads to mechanistic insights.
G3, published by the Genetics Society of America, meets the critical and growing need of the genetics community for rapid review and publication of important results in all areas of genetics. G3 offers the opportunity to publish the puzzling finding or to present unpublished results that may not have been submitted for review and publication due to a perceived lack of a potential high-impact finding. G3 has earned the DOAJ Seal, which is a mark of certification for open access journals, awarded by DOAJ to journals that achieve a high level of openness, adhere to Best Practice and high publishing standards.