Developmental NMDA receptor dysregulation in the infantile neuronal ceroid lipofuscinosis mouse model.

ABSTRACT: Protein palmitoylation and depalmitoylation alter protein function. This post-translational modification is critical for synaptic transmission and plasticity. Mutation of the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1) causes infantile neuronal ceroid lipofuscinosis (CLN1), a pediatric neurodegenerative disease. However, the role of protein depalmitoylation in synaptic maturation is unknown. Therefore, we studied synapse development in Ppt1^-/- mouse visual cortex. We demonstrate that the developmental N-methyl-D-aspartate receptor (NMDAR) subunit switch from GluN2B to GluN2A is stagnated in Ppt1^-/- mice. Correspondingly, Ppt1^-/- neurons exhibit immature evoked NMDAR currents and dendritic spine morphology in vivo. Fu

SUBMITTER: Koster KP 

PROVIDER: S-EPMC6464704 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature