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  2. Structural and expression analysis of the dopamine receptors reveals their crucial roles in regulating the insulin signaling pathway in oysters

Structural and expression analysis of the dopamine receptors reveals their crucial roles in regulating the insulin signaling pathway in oysters

  • Int J Biol Macromol. 2023 Jul 4;125703. doi: 10.1016/j.ijbiomac.2023.125703.
Yongjing Li 1 Ying Tan 1 Liting Ren 1 Qi Li 1 Jianxin Sui 2 Shikai Liu 3
Affiliations

Affiliations

  • 1 Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China.
  • 2 College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong 266003, China.
  • 3 Key Laboratory of Mariculture (Ocean University of China), Ministry of Education, College of Fisheries, Ocean University of China, Qingdao 266003, China. Electronic address: liushk@ouc.edu.cn.
Abstract

Dopamine performs its critical role upon binding to receptors. Since dopamine receptors are numerous and versatile, understanding their protein structures and evolution status, and identifying the key receptors involved in the modulation of Insulin signaling will provide essential clues to investigate the molecular mechanism of neuroendocrine regulating the growth in invertebrates. In this study, seven dopamine receptors were identified in the Pacific oysters (Crassostrea gigas) and were classified into four subtypes according to their protein secondary and tertiary structures, and ligand-binding activities. Of which, DR2 (Dopamine Receptor 2) and D(2)RA-like (D(2) Dopamine Receptor A-like) were considered the invertebrate-specific type 1 and type 2 dopamine receptors, respectively. Expression analysis indicated that the DR2 and D(2)RA-like were highly expressed in the fast-growing oyster "Haida No.1". After in vitro incubation of ganglia and adductor muscle with exogenous dopamine and Dopamine Receptor antagonists, the expressions of these two dopamine receptors and ILPs (insulin-like Peptides) were all significantly affected. Dual-fluorescence in situ hybridization results showed that D(2)RA-like and DR2 were co-localized with MIRP3 (molluscan insulin-related peptide 3) and MIRP3-like (molluscan insulin-related peptide 3-like) in the visceral ganglia, and were co-localized with ILP (insulin-like peptide) in the adductor muscle. Furthermore, the downstream components of dopamine signaling, including PKA, ERK, CREB, CaMKK1, Akt, and GSK3β were also significantly affected by the exogenous dopamine and Dopamine Receptor antagonists. These findings confirmed that dopamine might affect the secretion of ILPs through the invertebrate-specific dopamine receptors D(2)RA-like and DR2, and thus played crucial roles in the growth regulation of the Pacific oysters. Our study establishes the potential regulatory relationship between the dopaminergic system and insulin-like signaling pathway in marine invertebrates.

Keywords

Colocalization; Dopamine receptors; Growth regulation; Insulin-like peptides; Structural analysis.

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