Journal Article

Identification of C-Terminal Binding Protein 1 as a Novel NMDA Receptor Interactor

Stephenson, F Anne, Cousins, Sarah L

2019

Overview

A new N-methyl D aspartate neurotransmitter receptor interacting protein has been identified by yeast two-hybrid screening of a mouse brain cDNA library. C-terminal binding protein 1 (CtBP1) was shown to associate with the intracellular C-terminal regions of the N-methyl D aspartate receptor subunits GluN2A and GluN2D but not with GluN1-1a cytoplasmic C-terminal region. In yeast mating assays using a series of GluN2A C-terminal truncations, it was demonstrated that the CtBP1 binding domain was localized to GluN2A 1157–1382. The GluN2A binding domain was identified to lie within the CtBP1 161–224 region. CtBP1 co-immunoprecipitated with assembled GluN1/GluN2A receptors expressed in mammalian cells and also, in detergent extracts of adult mouse brain. Co-expression of CtBP1 with GluN1/GluN2A resulted in a significant decrease in receptor cell surface expression. The family of C-terminal binding proteins function primarily as transcriptional co-repressors. However, they are also known to modulate intracellular membrane trafficking mechanisms. Thus the results reported herein describe a putative role for CtBP1 in the regulation of cell surface N-methyl D aspartate receptor expression.

• Publisher: Springer Nature B.V
• Subject: Brain / Cell surface / Glutamic acid receptors (ionotropic) / Intracellular / Mammalian cells / Membrane trafficking / N-Methyl-D-aspartic acid receptors / Proteins / Receptors / Repressors / Transcription factors / Yeast