Abstract:
The evolutionary transition from diffusion-mediated cell-cell communication to faster, targeted synaptic signaling in animal nervous systems is still unclear. Genome sequencing analyses have revealed a widespread distribution of synapse-related genes among early-diverging metazoans, but how synaptic machinery evolved remains largely unknown. Here, we examine the function of neurexins (Nrxns), a family of presynaptic cell adhesion molecules with critical roles in bilaterian chemical synapses, using the cnidarian model, Nematostella vectensis. Delta-Nrxns are expressed mainly in neuronal cell clusters that exhibit both peptidergic and classical neurotransmitter signaling. Knockdown of δ-Nrxn reduces spontaneous peristalsis of N. vectensis polyps. Interestingly, gene knockdown and pharmacological studies suggest that δ-Nrxn is involved in glutamate- and glycine-mediated signaling rather than peptidergic signaling. Knockdown of the epithelial α-Nrxn reveals a major role in cell adhesion between ectodermal and endodermal epithelia. Overall, this study provides molecular, functional, and cellular insights into the pre-neural function of Nrxns, as well as key information for understanding how and why they were recruited to the synaptic machinery.
摘要:
从扩散介导的细胞-细胞通讯到更快的进化过渡,动物神经系统中的靶向突触信号仍不清楚。基因组测序分析揭示了突触相关基因在早期分化的后生动物中的广泛分布,但是突触机制是如何进化的仍然是未知的。这里,我们检查神经素(Nrxns)的功能,一个在双侧化学突触中起关键作用的突触前细胞粘附分子家族,使用cnidarian模型,线虫。Delta-Nrxns主要在显示肽能和经典神经递质信号的神经元细胞簇中表达。δ-Nrxn的击倒减少了N.vectensis息肉的自发蠕动。有趣的是,基因敲低和药理学研究表明,δ-Nrxn参与谷氨酸和甘氨酸介导的信号传导,而不是肽能信号传导.上皮α-Nrxn的敲低揭示了外胚层和内胚层上皮之间的细胞粘附的主要作用。总的来说,这项研究提供了分子,功能,以及对Nrxns前神经功能的细胞洞察,以及了解他们如何以及为什么被招募到突触机制的关键信息。