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Phospholipase C, Ca2+, and calmodulin signaling are required for 5-HT2A receptor-mediated transamidation of Rac1 by transglutaminase
dc.contributor.author | Dai, Ying | |
dc.contributor.author | Dudek, Nichole | |
dc.contributor.author | Li, Qian | |
dc.contributor.author | Muma, Nancy A. | |
dc.date.accessioned | 2017-06-28T19:22:09Z | |
dc.date.available | 2017-06-28T19:22:09Z | |
dc.date.issued | 2011-02 | |
dc.identifier.citation | Dai, Y., Dudek, N. L., Li, Q., & Muma, N. A. (2011). Phospholipase C, Ca2+, and calmodulin signaling are required for 5-HT2A receptor-mediated transamidation of Rac1 by transglutaminase. Psychopharmacology, 213(2-3), 403–412. http://doi.org/10.1007/s00213-010-1984-7 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24689 | |
dc.description.abstract | RATIONALE: Serotonin and especially serotonin 2A (5-HT2A) receptor signaling are important in the etiology and treatment of schizophrenia and affective disorders. We previously reported a novel 5-HT2A receptor effector, increased transglutaminase (TGase)-catalyzed transamidation, and activation of the small G protein Rac1 in A1A1v cells, a rat embryonic cortical cell line. OBJECTIVES: In this study, we explore the signaling pathway involved in 5-HT2A receptor-mediated Rac1 transamidation. METHODS: A1A1v cells were pretreated with pharmacological inhibitors of phospholipase C (PLC) or calmodulin (CaM), and then stimulated by the 5-HT2A receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI). Intracellular Ca2+ concentration and TGase-modified Rac1 transamidation were monitored. The effect of manipulation of intracellular Ca2+ by a Ca2+ ionophore or a chelating agent on Rac1 transamidation was also evaluated. RESULTS: In cells pretreated with a PLC inhibitor U73122, DOI-stimulated increases in the intracellular Ca2+ concentration and TGase-modified Rac1 were significantly attenuated as compared to those pretreated with U73343, an inactive analog. The membrane-permeant Ca2+ chelator, BAPTA-AM strongly reduced TGase-catalyzed Rac1 transamidation upon DOI stimulation. Conversely, the Ca2+ ionophore ionomycin, at a concentration that induced an elevation of cytosolic Ca2+ to a level comparable to cells treated with DOI, produced an increase in TGase-modified Rac1 without 5-HT2A receptor activation. Moreover, the CaM inhibitor W-7, significantly decreased Rac1 transamidation in a dose-dependent manner in DOI-treated cells. CONCLUSIONS: These results indicate that 5-HT2A receptorcoupled PLC activation and subsequent Ca2+ and CaM signaling are necessary for TGase-catalyzed Rac1 transamidation, and an increase in intracellular Ca2+ is sufficient to induce Rac1 transamidation. | 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 4.0 (CC BY-NC-ND 4.0), 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 | 5-HT2A receptor | en_US |
dc.subject | Rac1 | en_US |
dc.subject | Transglutaminase | en_US |
dc.subject | Transamidation | en_US |
dc.subject | Phospholipase C | en_US |
dc.subject | Calcium | en_US |
dc.subject | Calmodulin | en_US |
dc.subject | Serotonin | en_US |
dc.subject | Small G proteins | en_US |
dc.subject | A1A1v cells | en_US |
dc.subject | Serotonylation | en_US |
dc.title | Phospholipase C, Ca2+, and calmodulin signaling are required for 5-HT2A receptor-mediated transamidation of Rac1 by transglutaminase | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Li, Qian | |
kusw.kuauthor | Muma, Nancy A. | |
kusw.kudepartment | Pharmacy | en_US |
dc.identifier.doi | 10.1007/s00213-010-1984-7 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC3033764 | 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 4.0 (CC BY-NC-ND 4.0), 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.