Palmitoylation of the Parkinson's disease-associated protein synaptotagmin-11 links its turnover to α-synuclein homeostasis.

ABSTRACT: Synaptotagmin-11 (Syt11) is a vesicle-trafficking protein that is linked genetically to Parkinson's disease (PD). Likewise, the protein α-synuclein regulates vesicle trafficking, and its abnormal aggregation in neurons is the defining cytopathology of PD. Because of their functional similarities in the same disease context, we investigated whether the two proteins were connected. We found that Syt11 was palmitoylated in mouse and human brain tissue and in cultured cortical neurons and that this modification to Syt11 disrupted α-synuclein homeostasis in neurons. Palmitoylation of two cysteines adjacent to the transmembrane domain, Cys³⁹ and Cys⁴⁰, localized Syt11 to digitonin-insoluble portions of intracellular membranes and protected it from degradation by the endolys

SUBMITTER: Ho GPH 

PROVIDER: S-EPMC10150695 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature