Home | My Profile | Contact Us
Research Trends Products  |   order gateway  |   author gateway  |   editor gateway  
Register | Forgot Password

Author Resources
 Author Gateway
 Article submission guidelines

Editor Resources
 Editor/Referee Gateway

 Regional Subscription Agents/Distributors
Current Topics in Biochemical Research   Volumes    Volume 20 
Association with serotonin transporter enables the phosphorylation of insulin receptor in placenta
Fusun Kilic, Imane Moutkine, Luc Maroteaux
Pages: 65 - 78
Number of pages: 14
Current Topics in Biochemical Research
Volume 20 

Copyright © 2019 Research Trends. All rights reserved

Upon binding to insulin, the β-subunit of insulin receptor (IR) is phosphorylated and instantly activates intracellular signaling. A defect in this process causes the development of several metabolic disorders including non-insulin-dependent diabetes, such as type 2 and gestational diabetes mellitus (GDM). Under diabetic conditions the phosphorylation of IR in placenta, but not in platelets, is impaired. Interestingly the cellular distribution of the serotonin transporter (SERT), which utilizes the insulin signaling for posttranslational modification, shows tissue-type-dependent variation: SERT function is impaired in GDM-associated placenta, but not in platelets. In order to understand the correlation between IR, SERT and their tissue-type-dependent features, we tested an association between SERT and IR and whether this association affects the phosphorylation of IR. Using various approaches, we demonstrated a physical association between the Carboxyl terminal of SERT and the β-subunit of IR. This association was found on the plasma membrane of the placenta and the platelets. Next, the contribution of the SERT-IR association to the phosphorylation of IR was analyzed in heterologous and endogenous expression systems following insulin-treatment. The in vivo impact of SERT-IR association on the phosphorylation of IR was explored in placenta and platelets of SERT gene knockout (KO) mice. The IR phosphorylation was significantly downregulated only in the placenta, but not in platelets of SERT-KO mice. These findings are supported by time course experiments, which demonstrate that the phosphorylation of IR occurs vis-a-vis IR-SERT association, and at least one of the IR binding domains is identified as the carboxyl-terminus of SERT. These findings suggest an important role for IR-SERT association in maintaining the phosphorylation of IR and regulating the insulin signaling in placenta.
View Full Article  


Buy this article
Buy this volume
Subscribe to this title
Shopping Cart

Quick Links
Search Products
Browse in Alphabetical Order : Journals
Browse by Subject Classification : Journals

Ordering Information Ordering Information
Downloadable forms Downloadable Forms