The plasma membrane expression and glycosylation of serotonin transporter (SERT) protein in placental trophoblast, is highly dependent on an endoplasmic reticulum protein named ERp44. Initially, we identified that in gestational diabetes mellitus condition (GDM), ERp44 and SERT association is enhanced compared to non-diabetic trophoblast. This increased protein association in GDM inhibits SERT trafficking to the surface of the cell. As a result, the 5-HT uptake ability is reduced in GDM trophoblast compared to the non-diabetic sample. In addition, the retention of SERT via ERp44 leads to the formation of differentially glycosylated SERT protein in GDM trophoblast. Secondly, our results showed that the association between ERp44 and SERT can be reduced via insulin stimulation. However, the effect of insulin stimulation was only observed in non-diabetic trophoblast, which maintains proper insulin signaling via phosphorylation of AKT and S6K, but not in GDM trophoblast. Furthermore, insulin stimulation of non-diabetic trophoblast rescued surface SERT expression and the 5-HT uptake rate of trophoblast. Lastly, we demonstrated that there is a variation in insulin signaling response between trophoblast and platelets. This study provides a detailed insight on 5-HT mechanism and SERT location in non-diabetic and GDM trophoblast and platelets.
|Commitee:||Baldini, Giulia, Lowery, Curtis L., Lupashin, Vladimir V., Raney, Kevin D.|
|School:||University of Arkansas for Medical Sciences|
|Department:||Biochemistry and Molecular Biology|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 77/09(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Medicine, Pharmacology, Biochemistry, Physiology|
|Keywords:||Gestational diabetes mellitus, Serotonin transporter|
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