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

doi:10.1007/s12035-014-9085-y

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

PHA - Life and Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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
Pages (from-to)	1237-1246
Number of pages	10
Journal	Molecular Neurobiology
Volume	53
Issue number	2
DOIs	https://doi.org/10.1007/s12035-014-9085-y
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

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10.1007/s12035-014-9085-y

Cite this

Hong, L. J., Jiang, Q., Long, S., Wang, H., Zhang, L. D., Tian, Y., Wang, C. K., Cao, J. J., Tao, R. R., Huang, J. Y., Liao, M. H., Lu, Y. M., Fukunaga, K., Zhou, N. M., & Han, F. (2016). Valproic Acid Influences MTNR1A Intracellular Trafficking and Signaling in a β-Arrestin 2-Dependent Manner. Molecular Neurobiology, 53(2), 1237-1246. https://doi.org/10.1007/s12035-014-9085-y

Valproic Acid Influences MTNR1A Intracellular Trafficking and Signaling in a β-Arrestin 2-Dependent Manner. / Hong, Ling juan; Jiang, Quan; Long, Sen; Wang, Huan; Zhang, Ling di; Tian, Yun; Wang, Cheng kun; Cao, Jing jing; Tao, Rong rong; Huang, Ji yun; Liao, Mei hua; Lu, Ying mei; Fukunaga, Kohji; Zhou, Nai ming; Han, Feng.

In: Molecular Neurobiology, Vol. 53, No. 2, 01.03.2016, p. 1237-1246.

Research output: Contribution to journal › Article › peer-review

Hong, Ling juan ; Jiang, Quan ; Long, Sen ; Wang, Huan ; Zhang, Ling di ; Tian, Yun ; Wang, Cheng kun ; Cao, Jing jing ; Tao, Rong rong ; Huang, Ji yun ; Liao, Mei hua ; Lu, Ying mei ; Fukunaga, Kohji ; Zhou, Nai ming ; Han, Feng. / Valproic Acid Influences MTNR1A Intracellular Trafficking and Signaling in a β-Arrestin 2-Dependent Manner. In: Molecular Neurobiology. 2016 ; Vol. 53, No. 2. pp. 1237-1246.

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

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.",

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

note = "Funding Information: This work was supported by the National Natural Science Foundations of China (81402908, 81403024), Foundations of Hangzhou City Science and Technology Project (20130633B01), Foundations of Zhejiang Pharmaceutical Society (2013ZYY39), and Zhejiang Provincial Natural Science Foundation of China (LQ13H310001). Publisher Copyright: {\textcopyright} 2015, Springer Science+Business Media New York.",

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AU - Wang, Huan

AU - Zhang, Ling di

AU - Tian, Yun

AU - Wang, Cheng kun

AU - Cao, Jing jing

AU - Tao, Rong rong

AU - Huang, Ji yun

AU - Liao, Mei hua

AU - Lu, Ying mei

AU - Fukunaga, Kohji

AU - Zhou, Nai ming

AU - Han, Feng

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N2 - 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.

AB - 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.

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

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