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Article

Regulation of Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα

1
Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA
2
Department of Molecular Bioscience, College of Arts and Science, University of Kansas, Lawrence, KS 66045, USA
*
Author to whom correspondence should be addressed.
Co-first authors.
Academic Editors: Philippe De Deurwaerdere, Eric J. Vallender and Giuseppe Di Giovanni
Int. J. Mol. Sci. 2021, 22(24), 13176; https://doi.org/10.3390/ijms222413176
Received: 1 October 2021 / Revised: 21 November 2021 / Accepted: 2 December 2021 / Published: 7 December 2021
Serotonin 1A receptors (5-HT1ARs) are implicated in the control of mood, cognition, and memory and in various neuropsychiatric disorders such as depression and anxiety. As such, understanding the regulation of 5-HT1ARs will inform the development of better treatment approaches. We previously demonstrated 5-HT1ARs are SUMOylated by SUMO1 in the rat brain. Agonist stimulation increased SUMOylation and was further enhanced when combined with 17β-estradiol-3-benzoate (EB), which are treatments that cause the transient and prolonged desensitization of 5-HT1AR signaling, respectively. In the current study, we identified the protein inhibitor of activated STAT (PIAS)xα as the enzyme that facilitates SUMOylation, and SENP2 as the protein that catalyzes the deSUMOylation of 5-HT1ARs. We demonstrated that PIASxα significantly increased in the membrane fraction of rats co-treated with EB and an agonist, compared to either the EB-treated or vehicle-treated groups. The acute treatment with an agonist alone shifted the location of SENP2 from the membrane to the cytoplasmic fraction, but it has little effect on PIASxα. Hence, two separate mechanisms regulate SUMOylation and the activity of 5-HT1ARs by an agonist and EB. The effects of EB on 5-HT1AR SUMOylation and signaling may be related to the higher incidence of mood disorders in women during times with large fluctuations in estrogens. Targeting the SUMOylation of 5-HT1ARs could have important clinical relevance for the therapy for several neuropsychiatric disorders in which 5-HT1ARs are implicated. View Full-Text
Keywords: SUMOylation; PIAS; SENP; estrogen; estradiol; serotonin 1A receptors SUMOylation; PIAS; SENP; estrogen; estradiol; serotonin 1A receptors
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MDPI and ACS Style

Gupta, S.; Wang, M.; Azuma, Y.; Muma, N.A. Regulation of Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα. Int. J. Mol. Sci. 2021, 22, 13176. https://doi.org/10.3390/ijms222413176

AMA Style

Gupta S, Wang M, Azuma Y, Muma NA. Regulation of Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα. International Journal of Molecular Sciences. 2021; 22(24):13176. https://doi.org/10.3390/ijms222413176

Chicago/Turabian Style

Gupta, Sugandha, Mengya Wang, Yoshiaki Azuma, and Nancy A. Muma. 2021. "Regulation of Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα" International Journal of Molecular Sciences 22, no. 24: 13176. https://doi.org/10.3390/ijms222413176

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