Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis
Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis
复制标题
DOI：
10.1096/fj.201800274r
复制
发表时间：
2018-10-01
期刊：
影响因子：
4.8
通讯作者：
Jekely, Gaspar
中科院分区：
文献类型：
--
作者：
Schmidt, Axel;Bauknecht, Philipp;Jekely, Gaspar
神经肽通常通过代谢型GPCR发出信号。在一些软体动物和刺胞动物中，RFamide神经肽通过属于DEG/ENaC家族的肽门控离子通道介导快速离子型信号传导。在这里，我们描述了一个神经肽系统的双重模式的信号肽门控离子通道和GPCR。我们确定并表征了一个肽门控通道的海洋环节动物Platynereis dumerilii，是专门激活的Wamide myoinhibitory肽来自相同的proneuropeptide。肌抑制肽门控离子通道（MGIC）属于DEG/ENaC家族，与RFamide门控离子通道同源。我们测量了所有Wamides对MGIC和MAG的效力，并鉴定了优先激活一种或另一种受体的肽。单细胞转录组资源的分析表明MGIC和MAG信号在不同的靶神经元中。Wamide门控离子通道的鉴定表明，肽门控通道在动物中比以前认识到的更多样和广泛。神经肽信号通过离子型和代谢型受体传递到同一生物体中的不同靶细胞的可能性突出了肽能信号网络的额外复杂性水平。Bauknecht，P.，威廉姆斯，E.一、Augustinowski，K.，Grunder，S.，Jekely，G. Wamide肌抑制肽通过肽门控通道和GPCR在Platynereis中的双重信号传导。
Neuropeptides commonly signal by metabotropic GPCRs. In some mollusks and cnidarians, RFamide neuropeptides mediate fast ionotropic signaling by peptide-gated ion channels that belong to the DEG/ENaC family. Here we describe a neuropeptide system with a dual mode of signaling by both a peptide-gated ion channel and a GPCR. We identified and characterized a peptide-gated channel in the marine annelid Platynereis dumerilii that is specifically activated by Wamide myoinhibitory peptides derived from the same proneuropeptide. The myoinhibitory peptide-gated ion channel (MGIC) belongs to the DEG/ENaC family and is paralogous to RFamide-gated ion channels. Platynereis myoinhibitory peptides also activate a previously described GPCR, MAG. We measured the potency of all Wamides on both MGIC and MAG and identified peptides that preferentially activate one or the other receptor. Analysis of a single-cell transcriptome resource indicates that MGIC and MAG signal in distinct target neurons. The identification of a Wamide-gated ion channel suggests that peptide-gated channels are more diverse and widespread in animals than previously appreciated. The possibility of neuropeptide signaling by both ionotropic and metabotropic receptors to different target cells in the same organism highlights an additional level of complexity in peptidergic signaling networks.Schmidt, A., Bauknecht, P., Williams, E. A., Augustinowski, K., Grunder, S., Jekely, G. Dual signaling of Wamide myoinhibitory peptides through a peptide-gated channel and a GPCR in Platynereis.