赤拟谷盗蛛毒素受体Latrophilin的鉴定及其生理功能与进化适应性分析

蛛毒素受体Latrophilin (LPH) 不仅涉及人类与哺乳动物多动症、精神分裂症及成瘾等精神疾病的发生，还涉及到对外源蛛毒素的信号传递及多种药物的敏感性。但迄今对无脊椎动物LPH的功能及与脊椎动物LPH之间功能多样性形成、受体与配体的进化关系和信号传导机制研究不详。因此我们拟利用受体配体检测技术鉴定赤拟谷盗LPH的内、外源配体或通过免疫共沉淀鉴定其互作蛋白，并分析其能否介导特异性毒杀昆虫的蛛毒素信号而产生适应性。进而分析LPH对赤拟谷盗生长、发育的作用，及其对神经递质（乙酰胆碱、多巴胺）调控和药物（神经类药物与杀虫剂）效应之间的影响，并在转录水平和蛋白水平解析其下游信号传导网络。从而阐明赤拟谷盗LPH功能和调节机制，揭示物种特异性LPH受体与蛛毒素LTXs的进化机制，并为探讨LPH与杀虫剂的作用关系甚至发现新的生物杀虫剂靶标奠定基础。

Latrophilin (LPH) not only involved in the occurrence of schizophrenia, attention deficit/hyperactivity disorder as well as other diseases among humans and mammals, and could transmit exogenetic signal of latrotoxins (LTXs) in vertebrates as well as alter the sensitivity to some neurological disorder drug. However, up to date, it is unclear about the function of LPH in invertebrates, the mechanism of diversification of its multiple functions between invertebrates and vertebrates, co-evolution of the receptor and ligands, and their mechanism of signal transduction. Thus, we are planning to identify the insect specific endogenous and exogenetic ligands or the interactive proteins for LPH in Tribolium castaneum through the deorphanization method of GPCRs and CoIP methods, respectively, and dissect out whether the insect LPH could transduce the signal of latrotoxins which show specific lethal to insects, and how to generate the specific adaptivity. Furthermore, we will demonstrate the function of LPH on the growth, development of Tribolium castaneum, and analysis how it regulates the neurotransmitters (Acetylcoline and Dopamine) and involves in the drugs (Neurological disorder drugs and Insecticides) sensitivities. Moreover, we will illustrate the downstream signal transduction network in the transcriptional level and the protein level. Thus, it could illustrate the function and the regulation mechanism of LPH in Tribolium castaneum, and reveal the species-specific evolutionary mechanisms between LPH and LTXs. Furthermore, it could play fundamental roles in revealing the interaction between LPH and insecticides, even to discover the novel bio-insecticides which may target for LPH in the furture.