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

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 LRRK2 gene (nvLRRK2). The leucine rich repeat kinase 2 (LRRK2) gene, when mutated, is the most common cause of...

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Autores principales: Holmes, Grace, Ferguson, Sophie R., Lewis, Patrick Alfryn, Echeverri, Karen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659525/
https://www.ncbi.nlm.nih.gov/pubmed/37986927
http://dx.doi.org/10.21203/rs.3.rs-3525606/v1
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author Holmes, Grace
Ferguson, Sophie R.
Lewis, Patrick Alfryn
Echeverri, Karen
author_facet Holmes, Grace
Ferguson, Sophie R.
Lewis, Patrick Alfryn
Echeverri, Karen
author_sort Holmes, Grace
collection PubMed
description 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 LRRK2 gene (nvLRRK2). The leucine rich repeat kinase 2 (LRRK2) gene, when mutated, is the most common cause of inherited Parkinson’s Disease (PD). Its protein product (LRRK2) has implications in a variety of cellular processes, however, the full function of LRRK2 is not well established. Current research is focusing on understanding the function of LRRK2, including both its physiological role as well as its pathobiological underpinnings. METHODS: We used bioinformatics to determine the cross-species conservation of LRRK2, then applied drugs targeting the kinase activity of LRRK2 to examine its function in development, homeostasis and regeneration in Nematostella vectensis. RESULTS: An in-silico characterization and phylogenetic analysis of nvLRRK2 comparing it to human LRRK2 highlighted key conserved motifs and residues. 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 show a necessity for LRRK2 in development and regeneration. 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.
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spelling pubmed-106595252023-11-20 LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis Holmes, Grace Ferguson, Sophie R. Lewis, Patrick Alfryn Echeverri, Karen Res Sq Article 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 LRRK2 gene (nvLRRK2). The leucine rich repeat kinase 2 (LRRK2) gene, when mutated, is the most common cause of inherited Parkinson’s Disease (PD). Its protein product (LRRK2) has implications in a variety of cellular processes, however, the full function of LRRK2 is not well established. Current research is focusing on understanding the function of LRRK2, including both its physiological role as well as its pathobiological underpinnings. METHODS: We used bioinformatics to determine the cross-species conservation of LRRK2, then applied drugs targeting the kinase activity of LRRK2 to examine its function in development, homeostasis and regeneration in Nematostella vectensis. RESULTS: An in-silico characterization and phylogenetic analysis of nvLRRK2 comparing it to human LRRK2 highlighted key conserved motifs and residues. 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 show a necessity for LRRK2 in development and regeneration. 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. American Journal Experts 2023-11-07 /pmc/articles/PMC10659525/ /pubmed/37986927 http://dx.doi.org/10.21203/rs.3.rs-3525606/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Holmes, Grace
Ferguson, Sophie R.
Lewis, Patrick Alfryn
Echeverri, Karen
LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis
title LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis
title_full LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis
title_fullStr LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis
title_full_unstemmed LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis
title_short LRRK2 kinase activity is necessary for development and regeneration in Nematostella vectensis
title_sort lrrk2 kinase activity is necessary for development and regeneration in nematostella vectensis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659525/
https://www.ncbi.nlm.nih.gov/pubmed/37986927
http://dx.doi.org/10.21203/rs.3.rs-3525606/v1
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