Striatal spinophilin enhances D2R interaction with cytosolic proteins to mediate persistent D2R agonist-induced locomotor suppression.

ABSTRACT: Loss of dopamine neurons in Parkinson disease (PD) leads to motor deficits. Dopamine D2 receptor (D2R) agonists treat PD-associated motor deficits by acting on postsynaptic receptors located within the striatum that have been upregulated due dopamine loss. However, mechanisms that contribute to increased D2R activity in PD to enhance D2R function are poorly described. Spinophilin is a protein phosphatase 1 targeting protein that is expressed in postsynaptic dendritic spines and interacts with postsynaptic D2Rs. However, how spinophilin regulates D2R function is unknown. In the current study, we found that genetic knockout of spinophilin limited the suppression of locomotion caused by the D2R agonist, quinpirole. Mechanistically, we found that spinophilin is required for quinpirole-induced

SUBMITTER: Hens B 

PROVIDER: S-EPMC12458439 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature