Buchmann Institute for Molecular Life Sciences, Goethe University, Max-von-Laue-Strasse 15, D-60438, Frankfurt, Germany.
Department of Biochemistry, Chemistry and Pharmacy, Institute of Biophysical Chemistry, Goethe University, Frankfurt, Germany.
Nat Commun. 2024 Nov 3;15(1):9504. doi: 10.1038/s41467-024-53899-7.
Neuronal communication involves small-molecule transmitters, gap junctions, and neuropeptides. While neurons often express multiple neuropeptides, our understanding of the coordination of their actions and their mutual interactions remains limited. Here, we demonstrate that two neuropeptides, NLP-10 and FLP-1, released from the same interneuron pair, AVKL/R, exert antagonistic effects on locomotion speed in Caenorhabditis elegans. NLP-10 accelerates locomotion by activating the G protein-coupled receptor NPR-35 on premotor interneurons that promote forward movement. Notably, we establish that NLP-10 is crucial for the aversive response to mechanical and noxious light stimuli. Conversely, AVK-derived FLP-1 slows down locomotion by suppressing the secretion of NLP-10 from AVK, through autocrine feedback via activation of its receptor DMSR-7 in AVK neurons. Our findings suggest that peptidergic autocrine motifs, exemplified by the interaction between NLP-10 and FLP-1, might represent a widespread mechanism in nervous systems across species. These mutual functional interactions among peptidergic co-transmitters could fine-tune brain activity.
神经元通讯涉及小分子递质、缝隙连接和神经肽。虽然神经元通常表达多种神经肽，但我们对它们的作用协调及其相互作用的理解仍然有限。在这里，我们证明了来自同一中间神经元对（AVKL/R）的两种神经肽 NLP-10 和 FLP-1 对秀丽隐杆线虫的运动速度产生拮抗作用。NLP-10 通过激活促进前进运动的运动前中间神经元上的 G 蛋白偶联受体 NPR-35 来加速运动。值得注意的是，我们确定 NLP-10 对于对机械和有害光刺激的厌恶反应至关重要。相反，AVK 衍生的 FLP-1 通过激活 AVK 神经元中的其受体 DMSR-7，通过自分泌反馈抑制 AVK 中 NLP-10 的分泌，从而减缓运动速度。我们的发现表明，神经肽自分泌基序，例如 NLP-10 和 FLP-1 之间的相互作用，可能代表了跨物种神经系统中的一种广泛机制。这些神经肽共递质之间的相互功能相互作用可以微调大脑活动。
