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• W2039566040 startingPage "1843" @default.
• W2039566040 abstract "The plasma membrane 5-HT transporter (SERT) is the major protagonist in regulating extracellular 5-HT concentration and constitutes the target of drugs used to treat a host of metabolic and psychiatric disorders. The exact mechanisms sustaining SERT function still remain elusive. The present work exploits the properties of the 1C11 neuroectodermal progenitor, which acquires, upon 4 days of differentiation, a functional SERT within an integrated serotonergic phenotype to investigate regulatory mechanisms involved in SERT onset and functions. We show that poly(A) addition precedes SERT mRNA translation on day 2 of the serotonergic program. The newly translated transporter molecules immediately bind cocaine. Day 4 must be awaited to monitor antidepressant recognition and 5-HT uptake. Because external 5-HT reduces both 5-HT transport and SERT antidepressant binding, we identify 5-HT(2B) receptors as key players in controlling the overall 5-HT transport system. In the absence of external 5-HT, 5-HT(2B) receptor coupling to NO production ensures SERT phosphorylation to basal level and maximal 5-HT uptake. In the presence of 5-HT, the 5-HT(2B) receptor-PKC coupling promotes additional phosphorylations of both SERT and Na(+),K(+)-ATPase alpha-subunit, impairing the electrochemical gradient necessary to 5-HT uptake. SERT hyperphosphorylation also affects antidepressant recognition. Finally, such 5-HT(2B) receptor-mediated control of SERT activity operates in primary neurons from raphe nuclei. Altogether, our data shed new light on the 5-HT-driven post-translational modifications involved in the control of SERT activity." @default.
• W2039566040 created "2016-06-24" @default.
• W2039566040 creator A5036650816 @default.
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• W2039566040 date "2006-09-01" @default.
• W2039566040 modified "2023-10-04" @default.
• W2039566040 title "Serotonin transport and serotonin transporter‐mediated antidepressant recognition are controlled by 5‐HT_2Breceptor signaling in serotonergic neuronal cells" @default.
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• W2039566040 doi "https://doi.org/10.1096/fj.06-5724com" @default.
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