Serotonin 5-HT_2C Receptor Cys23Ser Single Nucleotide Polymorphism Associates with Receptor Function and Localization In Vitro.

ABSTRACT: A non-synonymous single nucleotide polymorphism of the human serotonin 5-HT_2C receptor (5-HT_2CR) gene that converts a cysteine to a serine at amino acid codon 23 (Cys23Ser) appears to impact 5-HT_2CR pharmacology at a cellular and systems level. We hypothesized that the Cys23Ser alters 5-HT_2CR intracellular signaling via changes in subcellular localization in vitro. Using cell lines stably expressing the wild-type Cys23 or the Ser23 variant, we show that 5-HT evokes intracellular calcium release with decreased potency and peak response in the Ser23 versus the Cys23 cell lines. Biochemical analyses demonstrated lower Ser23 5-HT_2CR plasma membrane localization versus the Cys23 5-HT_2CR. Subcellular localization studies demonstra

SUBMITTER: Land MA 

PROVIDER: S-EPMC6853916 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature