Estradiol potentiates 8-OH-DPAT-induced sumoylation of 5-HT1A receptor: characterization and subcellular distribution of sumoylated 5-HT1A receptors
dc.contributor.author | Li, Qian | |
dc.contributor.author | Muma, Nancy A. | |
dc.date.accessioned | 2017-02-22T18:17:20Z | |
dc.date.available | 2017-02-22T18:17:20Z | |
dc.date.issued | 2013-11 | |
dc.identifier.citation | Li, Q., & Muma, N. A. (2013). Estradiol potentiates 8-OH-DPAT-induced sumoylation of 5-HT1A receptor: characterization and subcellular distribution of sumoylated 5-HT1A receptors. Psychoneuroendocrinology, 38(11), 10.1016/j.psyneuen.2013.05.016. http://doi.org/10.1016/j.psyneuen.2013.05.016 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23219 | |
dc.description.abstract | Sumoylation is a recently described post-translational modification and only a few sumoylated neurotransmitter receptors are known. Through the present studies, we discovered that serotonin1A receptors (5-HT1A-Rs) can be sumoylated by SUMO1 (Small-Ubiquitin-related modifier 1) protein. The SUMO1-5-HT1A-R is ∼ 55kD, is located in the membrane fraction, but not the cytosol, and is distributed in all of the brain regions expressing 5-HT1A-Rs examined. Acute stimulation of 5-HT1A-Rs significantly increased SUMO1-5-HT1A-R in rat hypothalamus. Pre-treatment with estradiol for 2 days, which causes a partial desensitization of 5-HT1A-R signaling, potentiated agonistinduced increases in SUMO1-5-HT1A-Rs in the hypothalamus of ovariectomized rats. Using discontinuous gradient centrifugation followed by digitonin treatment, we found that the majority of SUMO1-5-HT1A-Rs is co-localized with endoplasmic-reticulum and trans-Golgi-network markers. Although a small proportion of SUMO1-5-HT1A-Rs are located in the detergent resistant microdomain (DRM) that contain active G-protein coupled receptors, their distribution was different from that of the Gαz protein that couples to the receptors. These data suggest that the SUMO1-5-HT1A-Rs are an inactive form of 5-HT1A-Rs, a finding further supported by results showing minimal 5-HT1A-R agonist binding to SUMO1-5-HT1A-Rs. Furthermore, SUMO1-5-HT1A-Rs in the DRM were increased by treatment with a 5-HT1A-R agonist, 8-OH-DPAT ((+)8-hydroxy-2-dipropylaminotetralin). Together, these data suggest that sumoylation of 5-HT1A-Rs may be related to 5-HT1A-R trafficking and internalization, which may contribute to 5-HT1A-R desensitization. Since 5-HT1A-Rs play an important role in mood regulation, the present results significantly impact on the understanding of the pathogenesis of affective disorders and development of better therapeutic approaches for these diseases. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | SUMO1 | en_US |
dc.subject | Endoplasmic reticulum | en_US |
dc.subject | Lipid raft | en_US |
dc.subject | Estradiol | en_US |
dc.subject | Fluoxetine | en_US |
dc.subject | Hypothalamus | en_US |
dc.title | Estradiol potentiates 8-OH-DPAT-induced sumoylation of 5-HT1A receptor: characterization and subcellular distribution of sumoylated 5-HT1A receptors | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Li, Qian | |
kusw.kuauthor | Muma, Nancy A. | |
kusw.kudepartment | Pharmacology and Toxicology | en_US |
dc.identifier.doi | 10.1016/j.psyneuen.2013.05.016 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.