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. 2021 Jun 3;15:677563. doi: 10.3389/fncel.2021.677563

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Copyright © 2021 Stilley and Blakely.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Model of receptor-mediated SERT regulation. Cell surface receptors like the adenosine receptor (A3AR) can regulate SERT via a protein kinase G (PKG) pathway that can both mobilize intracellular SERT proteins to move to the cell surface and, via a second, p38α MAPK-linked pathway, activate surface transporters to rapidly increase 5-HT transport rates. IL-1R stimulation by the inflammatory cytokine Il-1β can lead to SERT activation via PKG-independent p38α MAPK stimulation, without impacting SERT surface trafficking.