GSK-3β Interacts with Dopamine D1 Receptor to Regulate Receptor Function: Implication for Prefrontal Cortical D1 Receptor Dysfunction in Schizophrenia.

ABSTRACT:

Introduction

Impaired dopamine D1 receptor (D1R) function in prefrontal cortex (PFC) is believed to contribute to the PFC hypofunction that has been hypothesized to be associated with negative symptoms and cognitive deficits in schizophrenia. It is therefore critical to understand the mechanisms for modulation of D1R function.

Aims

To investigate the physical interaction and functional modulation between D1R and GSK-3β.

Results

D1R and GSK-3β physically interact in cultured cells and native brain tissues. This direct interaction was found to occur at the S(417)PALS(421) motif in the C-terminus of D1R. Inhibition of GSK-3β impaired D1R activation along with a decrease in D1R-GSK-3β interaction. GSK-3β inhibition reduced agonist-stimulated D1R desensitization and endocy

SUBMITTER: Wang JR 

PROVIDER: S-EPMC6492711 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature