在现存的原带体中是否存在黑色皮质蛋白受体?
Ren-Lei Ji1, Shan-Shan Jiang1, Gunnar Kleinau2
1Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.
Biomolecules
|September 28, 2024
概括
古老的带状受体,预测是黑色素皮质受体 (MCRs),缺乏MCR功能. 这些G蛋白结合受体 (GPCR) 具有构成性活性,但不结合已知的MCR配体,这表明它们具有新的功能.
科学领域:
- 进化生物学是进化的生物学.
- 分子药理学分子药理学
- 基因组学就是基因组学.
背景情况:
- 黑色皮质蛋白受体 (MCRs) 在脊椎动物中至关重要,但由于遗传数据有限,它们在早期带动物 (如头带动物和尿带动物) 中的存在是不确定的.
- 之前的研究在早期带动物 (循环带动物) 中确定了功能性MCR基因,突出了研究它们在更基本的带动物群体中的进化起源的必要性.
研究的目的:
- 为了研究MCR类受体在尿管和脑管中存在和功能.
- 为了确定早期带动物预测的MCR类受体是否表现出脊椎动物MCR的功能特征.
主要方法:
- 对来自 *Styela clava*, *Ciona intestinalis*, *Branchiostoma floridae* 和 *Branchiostoma belcheri* 的五个假定MCR类受体进行了生物信息分析 (BLAST,家族遗传分析).
- 实验验证,包括HEK 293T细胞中的受体表达,结合试验和对联体诱导的cAMP和ERK1/2信号的功能分析.
主要成果:
- 遗传学分析表明研究受体与脊椎动物MCR之间的关系,但关键的功能残留物不存在.
- 实验分析显示,与已知的MCR配体 (α-MSH,合成MC4R配体) 没有特定的结合或配体诱导信号 (cAMP,ERK1/2).
- 四个表达的受体显示出显著的基底cAMP信号,这表明了连接体独立的Gs合和构成性活性.
结论:
- 预测的五种MCR类受体是A类G蛋白合受体 (GPCR),但在连接体识别方面不起MCR的作用.
- 这些受体在Gs-cAMP通路中表现出高的构成性活性,这表明它们可能作为具有目前未识别的连接体的古老GPCR发挥作用.
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