尽管气体分子一氧化氮(NO)的信号调节动物的关键生理过程,包括收缩性,1-3豁免权,4,5发展,6-9和运动,10,11动物NO信号的早期进化仍不清楚。为了重建NO在动物茎谱系中的作用,我们着手研究鞭毛虫中的NO信号,动物的近亲。12在动物中,一氧化氮合酶(NOS)通过激活可溶性鸟苷酸环化酶(sGCs)通过cGMP规范地发出信号。13,14我们调查了NO信号通路成分在鞭毛虫多样性中的分布,发现了三种表达NOS的物种(细菌或真核来源),sGC,和先前显示参与NO/cGMP途径的下游基因。共表达sGCs和细菌型NOS的物种之一,Choanoecaflexa,我们发现,用NO处理可诱导cGMP合成和收缩。生化测定显示NO直接结合弯曲梭菌sGC1并刺激其环化酶活性。NO/cGMP途径独立于弯曲梭菌收缩的其他诱导剂,包括机械刺激和热量,但是光-暗转换诱导的收缩需要sGC活性。弯曲梭菌收缩中NO信号的输出导致从进食到游泳的转换,类似于海绵1-3和刺鼻动物中NO的作用,11,16,17,它中断进食并激活收缩力。这些数据为第一批动物的生物学和NO信号的进化提供了见解。
Although signaling by the gaseous molecule nitric oxide (NO) regulates key physiological processes in animals, including contractility,1-3 immunity,4,5 development,6-9 and locomotion,10,11 the early evolution of animal NO signaling remains unclear. To reconstruct the role of NO in the animal stem lineage, we set out to study NO signaling in
choanoflagellates, the closest living relatives of animals.12 In animals, NO produced by the nitric oxide synthase (NOS) canonically signals through cGMP by activating soluble guanylate cyclases (sGCs).13,14 We surveyed the distribution of the NO signaling pathway components across the diversity of
choanoflagellates and found three species that express NOS (of either bacterial or eukaryotic origin), sGCs, and downstream genes previously shown to be involved in the NO/cGMP pathway. One of the species coexpressing sGCs and a bacterial-type NOS, Choanoeca flexa, forms multicellular sheets that undergo collective contractions controlled by cGMP.15 We found that treatment with NO induces cGMP synthesis and contraction in C. flexa. Biochemical assays show that NO directly binds C. flexa sGC1 and stimulates its cyclase activity. The NO/cGMP pathway acts independently from other inducers of C. flexa contraction, including mechanical stimuli and heat, but sGC activity is required for contractions induced by light-to-dark transitions. The output of NO signaling in C. flexa-contractions resulting in a switch from feeding to swimming-resembles the effect of NO in sponges1-3 and cnidarians,11,16,17 where it interrupts feeding and activates contractility. These data provide insights into the biology of the first animals and the evolution of NO signaling.