LRRK2 interactions with microtubules are independent of LRRK2-mediated Rab phosphorylation

ABSTRACT: Deregulated microtubules are common defects associated with neurodegenerative diseases. Recent cryo-electron microscopy studies in cell lines overexpressing Parkinson's disease-associated LRRK2 suggest microtubule surfaces may regulate kinase activity by stabilizing different LRRK2 conformations. In macrophages with high endogenous LRRK2 expression, we find that nocodazole treatment destabilizes microtubules and impairs LRRK2-mediated Rab phosphorylation. GTP supplementation restores nocodazole-reduced Rab phosphorylation, linking LRRK2 kinase action to cellular GTP levels. Chemical microtubule stabilization, and kinetically trapping LRRK2 to microtubule surfaces, has negligible effects on Rab phosphorylation. In contrast, trapping LRRK2 to LAMP1-positive membranes upregulates LRRK2-media

SUBMITTER: Tuyana Malankhanova 

PROVIDER: S-SCDT-10_1038-S44319-025-00486-6 | biostudies-other |

REPOSITORIES: biostudies-other