LRRK2 kinase activity is necessary for development and regeneration inNematostella vectensis

Abstract

AbstractBackgroundThe 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.MethodsWe 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 inNematostella vectensis.ResultsAnin-silicocharacterization and phylogenetic analysis of nvLRRK2 comparing it to human LRRK2 highlighted key conserved motifs and residues.In vivoanalyses inhibiting the kinase function of this enzyme demonstrated a role of nvLRRK2 in development and regeneration ofN. vectensis. These findings implicate a developmental role of LRRK2 inNematostella, adding to the expanding knowledge of its physiological function.ConclusionsOur 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 introducesNematostella vectensisas a new model in which to study genes linked to neurodegenerative diseases such as Parkinson’s.