Abstract
Valproate exposure is associated with increased risks of autism spectrum disorder. To date, the mechanistic details of disturbance of melatonin receptor subtype 1 (MTNR1A) internalization upon valproate exposure remain elusive. By expressing epitope-tagged receptors (MTNR1A-EGFP) in HEK-293 and Neuro-2a cells, we recorded the dynamic changes of MTNR1A intracellular trafficking after melatonin treatment. Using time-lapse confocal microscopy, we showed in living cells that valproic acid interfered with the internalization kinetics of MTNR1A in the presence of melatonin. This attenuating effect was associated with a decrease in the phosphorylation of PKA (Thr197) and ERK (Thr202/Tyr204). VPA treatment did not alter the whole-cell currents of cells with or without melatonin. Furthermore, fluorescence resonance energy transfer imaging data demonstrated that valproic acid reduced the melatonin-initiated association between YFP-labeled β-arrestin 2 and CFP-labeled MTNR1A. Together, we suggest that valproic acid influences MTNR1A intracellular trafficking and signaling in a β-arrestin 2-dependent manner.
Original language | English |
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Pages (from-to) | 1237-1246 |
Number of pages | 10 |
Journal | Molecular Neurobiology |
Volume | 53 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2016 Mar 1 |
Keywords
- FRET
- Internalization
- Melatonin
- Melatonin receptor subtype 1
- Valproic acid
ASJC Scopus subject areas
- Neurology
- Cellular and Molecular Neuroscience