Synaptic NMDA Receptor Activation Induces Ubiquitination and Degradation of STEP₆₁.

ABSTRACT: NMDA receptor signaling is critical for the development of synaptic plasticity, learning, and memory, and dysregulation of NMDAR signaling is implicated in a number of neurological disorders including schizophrenia (SZ). Previous work has demonstrated that the STriatal-Enriched protein tyrosine Phosphatase 61 kDa (STEP₆₁) is elevated in human SZ postmortem cortical samples and after administration of psychotomimetics to cultures or mice. Here, we report that activation of synaptic NMDAR by bicuculline or D-serine results in the ubiquitination and proteasomal degradation of STEP₆₁, and increased surface localization of GluN1/GluN2B receptors. Moreover, bicuculline or D-serine treatments rescue the motor and cognitive deficits in MK-801-treated mice and reduce STEP

SUBMITTER: Xu J 

PROVIDER: S-EPMC5668205 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature