RRC ID 67476
Author Motoike S, Taguchi K, Harada K, Asano M, Hide I, Tanaka S, Irifune M, Sakai N.
Title Syntaxin 3 interacts with serotonin transporter and regulates its function.
Journal J Pharmacol Sci
Abstract Herein, we investigated the functional association of the serotonin transporter (SERT) with syntaxin-3 (STX3). We first overexpressed SERT and STX3 in various cells and examined their interaction, localization, and functional association. Immunoprecipitation studies revealed that STX3 interacted with SERT when expressed in COS-7 cells. Immunocytochemical studies revealed that SERT and STX3 were colocalized in the endoplasmic reticulum (ER) and Golgi apparatus. STX3 overexpression significantly reduced the uptake activity of SERT by attenuating its plasma membrane expression, suggesting that overexpressed STX3 anchors SERT in the ER and Golgi apparatus. STX3 knockdown did not affect the uptake activity of SERT but altered its glycosylation state. To elucidate the association of STX3 with SERT under physiological conditions, rather than overexpressing cells, we investigated this interaction in polarized Caco-2 cells, which endogenously express both proteins. Immunocytochemical studies revealed that SERT and STX3 were localized in microvilli-like structures at the apical plasma membrane. STX3 knockdown marginally but significantly decreased the serotonin uptake activity of Caco-2 cells, suggesting that STX3 positively regulates SERT function in Caco-2 cells, as opposed to SERT regulation by STX3 in overexpressing cells. Collectively, STX3 may colocalize with SERT during SERT membrane trafficking and regulate SERT function in an STX3-expressing lesion-dependent manner.
Volume 145(4)
Pages 297-307
Published 2021-4-1
DOI 10.1016/j.jphs.2021.01.007
PII S1347-8613(21)00008-6
PMID 33712280
MeSH Animals COS Cells Cell Membrane / metabolism Chlorocebus aethiops Endoplasmic Reticulum / metabolism Epistasis, Genetic / genetics* Gene Expression / genetics* Glycosylation Golgi Apparatus / metabolism Microvilli / metabolism Qa-SNARE Proteins / genetics Qa-SNARE Proteins / metabolism* Qa-SNARE Proteins / physiology* Serotonin Plasma Membrane Transport Proteins / genetics Serotonin Plasma Membrane Transport Proteins / metabolism* Serotonin Plasma Membrane Transport Proteins / physiology*
IF 2.835
Human and Animal Cells COS-7(RCB0539)