Abstract:
Teneurin C-terminal associated peptides (TCAP) are natural bioactive peptides that possess anxiety-reducing roles in animals, in vivo, and increase cell viability, in vitro. Although these peptides have some primary structural similarity to corticotropin-releasing factor (CRF), they are derived from the distal extracellular region of the teneurin transmembrane protein where they may act as separate soluble peptides after auto-catalytic cleavage from the teneurin protein following interaction with the cognate teneurin receptor, latrophilin (ADGRL), or expressed as a separate mRNA. However, although the signal transduction mechanism of TCAP in neurons has not been established, previous studies indicate an association with the intracellular calcium flux. Therefore, in this study, we have characterized the TCAP-mediated calcium response in hypothalamic cell lines using single-cell calcium methods with pharmacological antagonists to identify potential calcium channels, in vitro. Under normal circumstances, TCAP-1 reduces cytosolic calcium concentrations by uptake into the mitochondria and efflux through the plasma membrane independently of the teneurins. In doing so, TCAP-1 could inhibit the potential \'stress\' -inducing actions of CRF.
摘要:
TeneurinC端相关肽(TCAP)是天然的生物活性肽,在动物中具有减轻焦虑的作用,在体内,增加细胞活力,在体外。尽管这些肽与促肾上腺皮质激素释放因子(CRF)具有一些主要的结构相似性,它们来自teneurin跨膜蛋白的远端胞外区,在与同源teneurin受体相互作用后从teneurin蛋白自动催化裂解后,它们可以充当单独的可溶性肽,latrophilin(ADGRL),或表达为单独的mRNA。然而,虽然TCAP在神经元中的信号转导机制尚未建立,先前的研究表明与细胞内钙通量有关。因此,在这项研究中,我们使用单细胞钙方法和药理学拮抗剂鉴定了下丘脑细胞系中TCAP介导的钙反应,以鉴定潜在的钙通道,在体外。在正常情况下,TCAP-1通过摄取到线粒体中并通过质膜流出而独立于teneurin来降低细胞溶质钙浓度。在这样做的时候,TCAP-1可抑制CRF潜在的应激诱导作用。