Dynamic reversibility of α-synuclein serine-129 phosphorylation is impaired in synucleinopathy models

ABSTRACT: α-synuclein phosphorylation at serine-129 (pS129) is a widely used surrogate marker of pathology in Parkinson's disease and other synucleinopathies. However, we recently demonstrated that phosphorylation of S129 is also a physiological activator of synaptic transmission. In a feed-forward fashion, neuronal activity triggers reversible pS129. Here, we show that Parkinson's disease-linked missense mutations in SNCA impact activity-dependent pS129. Under basal conditions, cytosol-enriched A30P, H50Q, and G51D mutant forms of α-synuclein exhibit reduced pS129 levels in rat primary cortical neurons. A53T pS129 levels are similar to wild-type, and E46K pS129 levels are higher. A30P and E46K mutants show impaired reversibility of pS129 after stimulation. For the engineered profoundly membrane-as

SUBMITTER: Dr. Nagendran Ramalingam 

PROVIDER: S-SCDT-10_15252-EMBR_202357145 | biostudies-other |

REPOSITORIES: biostudies-other