Dopamine binds calmodulin during autoregulation of dopaminergic D2 receptor signaling through CaMKIIα-calmodulin complex
| Autor: | M O Olagunju, O V Obagaye, Babafemi J. Laoye, O A Okurumeh, O O Olubiyi, Oluwamolakun O. Bankole, Olalekan M. Ogundele |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Calmodulin Dopamine Heteromer Neurotransmission Pharmacology Molecular Dynamics Simulation Biochemistry Models Biological 03 medical and health sciences 0302 clinical medicine Dopamine receptor D1 Dopamine receptor D2 medicine Animals Homeostasis Molecular Biology Binding Sites biology Kinase Receptors Dopamine D2 Dopaminergic Cell Biology Cell biology Rats 030104 developmental biology biology.protein Thermodynamics Calcium-Calmodulin-Dependent Protein Kinase Type 2 030217 neurology & neurosurgery medicine.drug Protein Binding Signal Transduction |
| Zdroj: | Journal of receptor and signal transduction research. 36(3) |
| ISSN: | 1532-4281 |
| Popis: | The role of dopaminergic D2 receptor (D2R) autoregulation in dopamine (DA) neurotransmission cannot be overemphasized in cause and progression of disorders associated with complex behaviors. Although previous studies have shown that D2R is structurally and physiologically linked with calcium/calmodulin-dependent kinase II (CaMKIIα), however, the role of calmodulin in the CaMKIIα complex in D2R regulation remains elusive. In this study, using structural biology modeling softwares (iGEMDOCK and CueMol), we have shown the interaction between D2R, CaMKIIα, calmodulin, and DA under varying conditions. The outcomes of this study suggest that CaMKIIα causes a change in DA binding affinity to the D2R receptive site while the detached DA binds to calmodulin to stop the activity of D2R in the D2R-dopaminergic D1 receptor (D1R) heteromer. Ultimately, we concluded that D2R autoregulates to stop its heteromeric combination with D1R. D2R interacts with D1R to facilitate calcium movement that activates calmodulin, then CaMKIIα. The CaMKIIα-calmodulin complex changes the affinity of DA-D2R causing DA to break free and bind with calmodulin. |
| Databáze: | OpenAIRE |
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