Article
In-cell cryo-electron tomography reveals differential effects of type I and type II kinase inhibitors on LRRK2 filament formation and microtubule association.
eLife - 27 Jul 2026
Basiashvili Tamar, Hutchings Joshua, Chen Siyu, Karasmanis Eva P, Flaherty William Alexander, Leschziner Andres E, Villa Elizabeth
Abstract excerpt
Mutations in leucine-rich repeat kinase 2 (LRRK2) are a leading contributor to developing familial and idiopathic Parkinson's disease (PD). Most PD-causing LRRK2 mutations increase the kinase activity, leading to increased phosphorylation of Rab GTPases, disrupting vesicular trafficking, cytoskeletal dynamics, and autophagy. Under homeostatic conditions, the bulk of WT and PD-mutant LRRK2 is found in the cellular...
Topics
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
- Humans
- Microtubules
- HEK293 Cells
- Protein Kinase Inhibitors
- Electron Microscope Tomography
- Cryoelectron Microscopy
- Parkinson Disease
- Mutation
- Indazoles
- Pyrimidines