Valproic Acid Influences MTNR1A Intracellular Trafficking and Signaling in a β-Arrestin 2-Dependent Manner

Ling juan Hong, Quan Jiang, Sen Long, Huan Wang, Ling di Zhang, Yun Tian, Cheng kun Wang, Jing jing Cao, Rong rong Tao, Ji yun Huang, Mei hua Liao, Ying mei Lu, Kohji Fukunaga, Nai ming Zhou, Feng Han

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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 languageEnglish
Pages (from-to)1237-1246
Number of pages10
JournalMolecular Neurobiology
Issue number2
Publication statusPublished - 2016 Mar 1


  • FRET
  • Internalization
  • Melatonin
  • Melatonin receptor subtype 1
  • Valproic acid

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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