Holmes Grace, Ferguson Sophie R, Lewis Patrick Alfryn, Echeverri Karen
Royal Veterinary College, University of London, Camden, London, NW1 0TU, UK.
Marine Biological Laboratory, Eugene Bell Center for Regenerative Biology and Tissue Engineering, Woods Hole, MA, 02543, USA.
Neural Dev. 2024 Aug 8;19(1):16. doi: 10.1186/s13064-024-00193-3.
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.
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.
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.
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.
星状海葵（Nematostella vectensis）是一种新兴的模式生物，具有很高的再生能力，最近发现它拥有与人类富含亮氨酸重复激酶2（LRRK2）基因的同源物。该基因的突变是遗传性帕金森病（PD）最常见的病因，这凸显了了解其功能的重要性。然而，尽管经过了二十年的研究，LRRK2的功能仍未完全明确。
为了研究星状海葵中LRRKs的功能，我们应用了靶向LRRK2激酶活性的小分子抑制剂，以研究其在星状海葵发育、体内平衡和再生中的功能。
对该酶激酶功能的体内分析表明，nvLRRK2在星状海葵的发育和再生中发挥作用。这些发现暗示了LRRK2在星状海葵中的发育作用，增加了对其生理功能的认识。
我们的工作引入了一种新的模式生物来研究LRRK生物学。我们报告说，LRRK激酶活性对星状海葵的发育和再生是必要的。鉴于其短的世代时间、遗传可追踪性和体内成像能力，这项工作将星状海葵引入为一种新的模式生物，用于研究与帕金森病等神经退行性疾病相关的基因。
