Accumulation of LRRK2-associated phospho-Rab12 degenerative lysosomes in tauopathies.

ABSTRACT: Parkinson's disease (PD) pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with endolysosomal dysfunction across cell types, and carriers of LRRK2 mutations variably present with phosphorylated tau and α-synuclein deposits in post-mortem analysis. LRRK2 mutations increase the phosphorylation of Rab substrates including Rab12. Rab12 is expressed in neuronal and non-neuronal cells with localization to membranes in the endolysosomal compartment. Under lysosomal stress, LRRK2 interaction with Rab12 upregulates LRRK2 kinase activity. In this study, using a recently developed monoclonal antibody directed to the LRRK2-mediated phosphorylation site on Rab12 at amino acid Ser106 (pS106-Rab12), we test whether aberrant LRRK2 phosphorylation is as

SUBMITTER: Buck SA 

PROVIDER: S-EPMC12258990 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature