Reichhart Jean Marc, Gubb David, Leclerc Vincent
UPR 9022 CNRS, IBMC, Université de Strasbourg, 15 Rue Descartes, Strasbourg, France.
Methods Enzymol. 2011;499:205-25. doi: 10.1016/B978-0-12-386471-0.00011-0.
Members of the serpin superfamily of proteins have been found in all living organisms, although rarely in bacteria or fungi. They have been extensively studied in mammals, where many rapid physiological responses are regulated by inhibitory serpins. In addition to the inhibitory serpins, a large group of noninhibitory proteins with a conserved serpin fold have also been identified in mammals. These noninhibitory proteins have a wide range of functions, from storage proteins to molecular chaperones, hormone transporters, and tumor suppressors. In contrast, until recently, very little was known about insect serpins in general, or Drosophila serpins in particular. In the last decade, however, there has been an increasing interest in the serpin biology of insects. It is becoming clear that, like in mammals, a similar wide range of physiological responses are regulated in insects and that noninhibitory serpin-fold proteins also play key roles in insect biology. Drosophila is also an important model organism that can be used to study human pathologies (among which serpinopathies or other protein conformational diseases) and mechanisms of regulation of proteolytic cascades in health or to develop strategies for control of insect pests and disease vectors. As most of our knowledge on insect serpins comes from studies on the Drosophila immune response, we survey here the Drosophila serpin literature and describe the laboratory techniques that have been developed to study serpin-regulated responses in this model genetic organism.
丝氨酸蛋白酶抑制剂(serpin)超家族的蛋白质成员在所有生物中均有发现,不过在细菌或真菌中较为罕见。它们在哺乳动物中得到了广泛研究,许多快速的生理反应都由抑制性丝氨酸蛋白酶抑制剂调节。除了抑制性丝氨酸蛋白酶抑制剂外,在哺乳动物中还鉴定出了一大类具有保守丝氨酸蛋白酶抑制剂折叠结构的非抑制性蛋白质。这些非抑制性蛋白质具有广泛的功能,从储存蛋白到分子伴侣、激素转运蛋白和肿瘤抑制因子。相比之下,直到最近,人们对昆虫的丝氨酸蛋白酶抑制剂,尤其是果蝇的丝氨酸蛋白酶抑制剂总体上了解甚少。然而,在过去十年中,人们对昆虫丝氨酸蛋白酶抑制剂生物学的兴趣与日俱增。越来越清楚的是,与哺乳动物一样,昆虫中也有类似广泛的生理反应受到调节,并且非抑制性丝氨酸蛋白酶抑制剂折叠蛋白在昆虫生物学中也发挥着关键作用。果蝇也是一种重要的模式生物,可用于研究人类病理学(其中包括丝氨酸蛋白酶抑制剂病或其他蛋白质构象疾病)以及健康状态下蛋白水解级联反应的调节机制,或者开发控制害虫和疾病传播媒介的策略。由于我们对昆虫丝氨酸蛋白酶抑制剂的大部分了解都来自对果蝇免疫反应的研究,我们在此综述果蝇丝氨酸蛋白酶抑制剂的文献,并描述为研究这种模式遗传生物中丝氨酸蛋白酶抑制剂调节的反应而开发的实验室技术。