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

Holmes, Grace; Ferguson, Sophie R; Lewis, Patrick Alfryn; Echeverri, Karen; (2024) LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis. Neural Development , 19 , Article 16. 10.1186/s13064-024-00193-3. Green open access

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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.

Type: Article
Title: LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13064-024-00193-3
Publisher version: https://doi.org/10.1186/s13064-024-00193-3
Language: English
Additional information: This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Keywords: Nematostella vectensis, Development, Regeneration, LRRK
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10195852
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