LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis

Holmes, G; Ferguson, SR; Lewis, PA; Echeverri, K

Abstract

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.

Citation

Holmes, G., Ferguson, S., Lewis, P., & Echeverri, K. (2024). LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis. Neural Development, 19(1), https://doi.org/10.1186/s13064-024-00193-3

• Journal Article Type: Article
• Acceptance Date: Jul 23, 2024
• Online Publication Date: Aug 8, 2024
• Publication Date: 2024
• Deposit Date: Aug 20, 2024
• Publicly Available Date: Aug 20, 2024
• Print ISSN: 1749-8104
• Electronic ISSN: 1749-8104
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 1
• DOI: https://doi.org/10.1186/s13064-024-00193-3
• Keywords: Nematostella vectensis; Development; Regeneration; LRRK; STARLET SEA-ANEMONE; PARKINSONS-DISEASE; GENE; EVOLUTION; MODEL; NEUROGENESIS; EXPRESSION; INHIBITORS; MUTATION; SYSTEM