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

BACKGROUND

The starlet sea anemone, 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 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

RESULTS

An characterization and phylogenetic analysis of nvLRRK2 comparing it to human LRRK2 highlighted key conserved motifs and residues. analyses inhibiting the kinase function of this enzyme demonstrated a role of nvLRRK2 in development and regeneration of These findings implicate a developmental role of LRRK2 in 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 as a new model in which to study genes linked to neurodegenerative diseases such as Parkinson's.