Receptor-stimulated transamidation induces activation of Rac1 and Cdc42 and the regulation of dendritic spines
| Autor: | Qian Li, Zhen Mi, Tuda Si, Khushboo Kapadia, Nancy A. Muma |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
rac1 GTP-Binding Protein
0301 basic medicine RHOA Dendritic spine Dendritic Spines Primary Cell Culture Serotonylation Stimulation Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Muscarinic acetylcholine receptor Animals Humans Receptor Serotonin 5-HT2A cdc42 GTP-Binding Protein Receptor 5-HT receptor Pharmacology Transglutaminases biology Amphetamines Cell biology 030104 developmental biology Biochemistry biology.protein Signal transduction rhoA GTP-Binding Protein Serotonin 5-HT2 Receptor Agonists 030217 neurology & neurosurgery |
| Zdroj: | Neuropharmacology. 117:93-105 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/j.neuropharm.2017.01.034 |
| Popis: | Regulation of dendritic spines is an important component of synaptic function and plasticity whereas dendritic spine dysregulation is related to several psychiatric and neurological diseases. In the present study, we tested the hypothesis that serotonin (5-HT)2A/2C receptor-induced Rho family transamidation and activation regulates dendritic spine morphology and that activation of multiple types of receptors can induce transglutaminase (TGase)-catalyzed transamidation of small G proteins. We previously reported a novel 5-HT2A receptor downstream effector, TGase-catalyzed serotonylation of the small G protein Rac1 in A1A1v cells, a rat embryonic cortical cell line. We now extend these findings to rat primary cortical cultures which develop dendritic spines; stimulation of 5-HT2A/2C receptors increased transamidation of Rac1 and Cdc42, but not RhoA. Inhibition of TGases significantly decreased transamidation and activation of Rac1 and Cdc42, suggesting that transamidation led to their activation. In primary cortical cultures, stimulation of 5-HT2A/2C receptors by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) caused a transient dendritic spine enlargement, which was blocked by TGase inhibition. Stimulation of both 5-HT2A and 5-HT2C receptors contributed to DOI-induced Rac1 transamidation in primary cortical cultures as demonstrated by selective antagonists. Furthermore, stimulation of muscarinic acetylcholine receptors and NMDA receptors also increased TGase-catalyzed Rac1 activation in SH-SY5Y cells and N2a cells, respectively. Receptor-stimulated TGase-catalyzed transamidation of Rac1 occurs at Q61, a site previously reported to be important in the inactivation of Rac1. These studies demonstrate that TGase-catalyzed transamidation and activation of small G proteins results from stimulation of multiple types of receptors and this novel signaling pathway can regulate dendritic spine morphology and plasticity. |
| Databáze: | OpenAIRE |
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