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 STEP61 in mouse frontal cortex. These results suggest that STEP61 may contribute to the therapeutic effects of D-serine.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Xu J,Kurup P,Nairn AC,Lombroso PJ

doi

10.1007/s12035-017-0555-x

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

3096-3111

issue

4

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-017-0555-x

journal_volume

55

pub_type

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