title: Dopamine binds calmodulin during autoregulation of dopaminergic D2 receptor signaling through CaMKIIα-calmodulin complex.
abstract: 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.
authors.affiliation: a Department of Biological Sciences , College of Sciences, Afe Babalola University , Ado-Ekiti , Nigeria .
authors.forename: B J
authors.initials: BJ
authors.lastname: Laoye
authors.affiliation: b Department of Mathematical and Physical Sciences , College of Sciences, Afe Babalola University , Ado-Ekiti , Nigeria .
authors.forename: O A
authors.initials: OA
authors.lastname: Okurumeh
authors.affiliation: c Cell Biology and Biotechnology Program; Department of Biological Sciences, College of Sciences, Afe Babalola University , Ado-Ekiti , Nigeria .
authors.forename: O V
authors.initials: OV
authors.lastname: Obagaye
authors.affiliation: c Cell Biology and Biotechnology Program; Department of Biological Sciences, College of Sciences, Afe Babalola University , Ado-Ekiti , Nigeria .
authors.forename: M O
authors.initials: MO
authors.lastname: Olagunju
authors.affiliation: a Department of Biological Sciences , College of Sciences, Afe Babalola University , Ado-Ekiti , Nigeria .
authors.forename: O O
authors.initials: OO
authors.lastname: Bankole
authors.affiliation: e Department of Anatomy , Neural Systems Laboratory, College of Medicine and Health Sciences, Afe Babalola University , Ado-Ekiti , Nigeria.
authors.forename: O O
authors.initials: OO
authors.lastname: Olubiyi
authors.affiliation: d Department of Pharmacology , College of Medicine and Health Sciences, Afe Babalola University , Ado-Ekiti , Nigeria , and.
authors.forename: O M
authors.initials: OM
authors.lastname: Ogundele
mesh_terms: D000818:Animals; D001665:Binding Sites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism*; D004298:Dopamine / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D013816:Thermodynamics
chemical_list: D002147:Calmodulin; D017448:Receptors, Dopamine D2; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D004298:Dopamine
keywords: Autoregulation; CaMKIIα; D2R; calcium; calmodulin; dopamine