The Role of LRRK2 in Intracellular Organelle Dynamics

J Mol Biol. 2023 Jun 15;435(12):167998. doi: 10.1016/j.jmb.2023.167998. Epub 2023 Feb 9.

Abstract

Pathogenic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene hyperactivate LRRK2 kinase activity and lead to the development of Parkinson's disease (PD). Membrane recruitment of LRRK2 and the identification of RAB GTPases as bona fide LRRK2 substrates strongly indicate that LRRK2 regulates intracellular trafficking. This review highlights the current literature on the role of LRRK2 in intracellular organelle dynamics. With a focus on the effects of LRRK2 on microtubule function, mitochondrial dynamics, the autophagy-lysosomal pathway, and synaptic vesicle trafficking, it summarizes our current understanding of how intracellular dynamics are altered upon pathogenic LRRK2 hyperactivation.

Keywords: Autophagosomes; Lysosomes; Mitochondria; Parkinson’s disease; RAB GTPases.

Publication types

  • Review

MeSH terms

  • Autophagy
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2* / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2* / metabolism
  • Lysosomes* / metabolism
  • Mutation
  • Parkinson Disease* / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism

Substances

  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • LRRK2 protein, human
  • rab GTP-Binding Proteins