Molecular Developmental Physiology and Signal Transduction, KU Leuven, Naamsestraat 59, P.O. Box 2465, B-3000 Leuven, Belgium.
Laboratory of Cellular Transport Systems, ON I, Herestraat 49, P.O. Box 802, B-3000 Leuven, Belgium.
Int J Mol Sci. 2021 Dec 15;22(24):13465. doi: 10.3390/ijms222413465.
Accurate control of innate behaviors associated with developmental transitions requires functional integration of hormonal and neural signals. Insect molting is regulated by a set of neuropeptides, which trigger periodic pulses in ecdysteroid hormone titers and coordinate shedding of the old cuticle during ecdysis. In the current study, we demonstrate that crustacean cardioactive peptide (CCAP), a structurally conserved neuropeptide described to induce the ecdysis motor program, also exhibits a previously unknown prothoracicostatic activity to regulate ecdysteroid production in the desert locust, . We identified the locust genes encoding the CCAP precursor and three G protein-coupled receptors that are activated by CCAP with EC values in the (sub)nanomolar range. Spatiotemporal expression profiles of the receptors revealed expression in the prothoracic glands, the endocrine organs where ecdysteroidogenesis occurs. RNAi-mediated knockdown of CCAP precursor or receptors resulted in significantly elevated transcript levels of several genes, which encode ecdysteroid biosynthesis enzymes, and in elevated ecdysteroid levels one day prior to ecdysis. Moreover, prothoracic gland explants exhibited decreased secretion of ecdysteroids in the presence of CCAP. Our results unequivocally identify CCAP as the first prothoracicostatic peptide discovered in a hemimetabolan species and reveal the existence of an intricate interplay between CCAP signaling and ecdysteroidogenesis.
准确控制与发育转变相关的先天行为需要激素和神经信号的功能整合。昆虫蜕皮受一组神经肽调节，这些神经肽触发蜕皮激素水平的周期性脉冲，并协调蜕皮期间旧表皮的脱落。在本研究中，我们证明了甲壳动物心脏活性肽（CCAP），一种结构保守的神经肽，被描述为诱导蜕皮运动程序，也表现出以前未知的前胸腺抑制活性，以调节沙漠蝗， 蜕皮激素的产生。我们鉴定了编码 CCAP 前体的基因和三个 G 蛋白偶联受体，这些受体被 CCAP 以 EC 值在（亚）纳摩尔范围内激活。受体的时空表达谱显示在前胸腺中的表达，前胸腺是发生蜕皮激素发生的内分泌器官。CCAP 前体或受体的 RNAi 介导的敲低导致几种编码蜕皮激素生物合成酶的基因的转录水平显著升高，并且在蜕皮前一天升高。此外，前胸腺外植体在 CCAP 的存在下表现出蜕皮激素分泌减少。我们的研究结果明确地将 CCAP 鉴定为在半变态物种中发现的第一个前胸腺抑制肽，并揭示了 CCAP 信号与蜕皮激素发生之间存在复杂的相互作用。
