背景:小星星海葵,线虫,是一种具有高再生能力的新兴模式生物,最近发现它具有人类富含亮氨酸的重复激酶2(LRRK2)基因的直向同源物。该基因的突变是遗传性帕金森病(PD)的最常见原因,强调理解其功能的重要性。尽管经过二十年的研究,然而,LRRK2的功能尚未完全确定。
方法:为了研究LRRKs在线虫中的作用,我们应用小分子抑制剂靶向LRRK2的激酶活性,以检查其在发育中的功能,线虫的稳态和再生。
结果:抑制该酶的激酶功能的体内分析证明了nvLRRK2在N.vectensis的发育和再生中的作用。这些发现暗示LRRK2在线虫中的发育作用,增加了对其生理功能的了解。
结论:我们的工作引入了一种新的模型生物来研究LRRK生物学。我们报告说,LRRK激酶活性对于线虫的发育和再生是必需的。由于生成时间短,遗传跟踪能力和体内成像能力,这项工作介绍了Nematostellavectensis作为一个新的模型,研究与神经退行性疾病相关的基因,如帕金森氏症。
BACKGROUND: The starlet sea anemone, Nematostella vectensis, is an emerging model organism with a high regenerative capacity, which was recently found to possess an orthologue to the human Leucine Rich Repeat Kinase 2 (LRRK2) gene. Mutations in this gene are the most common cause of inherited Parkinson\'s Disease (PD), highlighting the importance of understanding its function. Despite two decades of research, however, the function of LRRK2 is not well established.
METHODS: To investigate the function of LRRKs in Nematostella vectensis, we applied small molecule inhibitors targeting the kinase activity of LRRK2 to examine its function in development, homeostasis and regeneration in Nematostella vectensis.
RESULTS: In vivo analyses inhibiting the kinase function of this enzyme demonstrated a role of nvLRRK2 in development and regeneration of N. vectensis. These findings implicate a developmental role of LRRK2 in Nematostella, adding to the expanding knowledge of its physiological function.
CONCLUSIONS: Our work introduces a new model organism with which to study LRRK biology. We report that LRRK kinase activity is necessary for the development and regeneration of Nematostella. Given the short generation time, genetic trackability and in vivo imaging capabilities, this work introduces Nematostella vectensis as a new model in which to study genes linked to neurodegenerative diseases such as Parkinson\'s.