家蚕短神经肽F受体家族新成员的分子鉴定及信号转导机制初探

Short neuropeptide Fs (sNPFs) belong to the neuropeptide Y/neuropeptide F superfamily, and consist of 6-11 amino acids that are characterized by the conserved C-terminal sequence RLRFamide or RLRWamide. sNPFs may play critical roles in many physiological processes including feeding and growth, clock function, hormone release, as well as learning and memory，but the related molecular mechanisms remains largely unknown.The physiological functions of sNPF are mediated by its membrane receptors, belonging to G-protein coupled receptors. Binding of peptide to receptor initiates a series of events which leads to changes of second messengers(Ca2+,cAMP) within the cell,and then trigger a series of molecular interactions that alter the physiologic state of the cell.So identification of sNPF-activated receptors is essential for regarding the regulatory mechanisms underlying sNPF mediated signal pathways.Our preliminary studies identified a novel orphan G-protein coupled receptor(GPCR) also can be activated by Bombyx sNPFs with higher affinity in Bombyx mori，called as Bombyx neuropeptide GPCR A7(BNGR-A7).This is a breakthrough in sNPF related research fields,because only two sNPF receptors (BNGR-A10/A11) have been identified by previous studies in Bombyx.Our preliminary findings will provide a platform to investigate the nature of molecular mechanisms underlying sNPF-involved functions, also be helpful for understanding of novel physiological functions of sNPF in insects. Based on our existing research results, we look forward to conducting in-depth study of signal transduction mechanisms underlying sNPF-involved pathways ,to clarify its physiological regulation of Bombyx mori. This project will give us better understanding of regulatory mechanisms and to explore the new physiological functions of sNPF peptides. The results can also help us to generate insect control agents based on sNPF receptors antagonists and provide theorical foundation for related research in human beings.

短神经肽F（sNPF）是一类具有6-11个氨基酸残基的小肽，在家蚕体内可能参与调控进食、生长发育、生物钟、激素释放、产丝、认知等重要生理过程，但其受体系统及相关调控机制尚不清楚。我们利用过表达系统研究发现：家蚕"孤儿受体"BNGR-A7 受到sNPF刺激后，胞内第二信使cAMP水平发生显著变化，且能够诱导ERK通路激活与受体内吞，故推断BNGR-A7可能是sNPF新受体。我们拟根据这一新发现利用细胞生物学手段系统证实BNGR-A7为sNPF受体，揭示家蚕sNPF 受体家族的信号转导及调控机制，并探索其新的生理功能。本课题不仅有助于提高家蚕作为经济昆虫的农业价值，为研发安全有效、无公害的农药提供理论依据；而且家蚕作为模式动物，其信号转导的调控机制具有普遍的生物学意义，可为人类相关研究提供参考。

短神经肽F（sNPF）是一类具有6-11 个氨基酸残基的小肽，在家蚕体内可能参与调控进食、生长发育、生物钟、激素释放、产丝、认知等重要生理过程，但其受体系统及相关调控机制尚不清楚。本研究组利用生物信息学技术种群交叉分析推测家蚕“孤儿受体”（未找到其天然配体的受体）BNGR-A7 可能也是sNPF 的受体，此分析源于我们研究组成功发现并证实孤儿受体BNGR-A28/A29 为家蚕另一类神经肽受体---脂动激素受体（AKHR）家族新成员的研究。实验结果证实了我们的推断，孤儿受体BNGR-A7 在受到sNPF 刺激后，细胞内第二信使cAMP 水平发生明显变化，且能够诱导ERK 通路激活，并通过结合实验证实BNGR-A7是sNPF 新受体。本课题不仅有助于提高家蚕作为经济昆虫的农业价值，为研发安全有效、无公害的农药提供理论依据；而且家蚕作为模式动物，其信号转导的调控机制具有普遍的生物学意义，可为人类相关研究提供参考。