title: Wnt5a-dopamine D2 receptor interactions regulate dopamine neuron development via extracellular signal-regulated kinase (ERK) activation.
abstract: The dopamine D2 receptor (D2R) plays an important role in mesencephalic dopaminergic neuronal development, particularly coupled with extracellular signal-regulated kinase (ERK) activation. Wnt5a protein is known to regulate the development of dopaminergic neurons. We analyzed the effect of Wnt5a on dopaminergic neuron development in mesencephalic primary cultures from wild-type (WT) and D2R knock-out (D2R(-/-)) mice. Treatment with Wnt5a increased the number and neuritic length of dopamine neurons in primary mesencephalic neuronal cultures from WT mice, but not from D2R(-/-) mice. The effect of Wnt5a was completely blocked by treatment with D2R antagonist or inhibitors of MAPK or EGFR. Wnt5a-mediated ERK activation in mesencephalic neuronal cultures was inhibited by treatment of D2R antagonist and EGFR inhibitors in WT mice. However, these regulations were not observed for D2R(-/-) mice. Co-immunoprecipitation and displacement of [(3)H]spiperone from D2R by Wnt5a demonstrated that Wnt5a could bind with D2R. This interaction was confirmed by GST pulldown assays demonstrating that the domain including transmembrane domain 4, second extracellular loop, and transmembrane domain 5 of D2R binds to Wnt5a. These results suggest that the interaction between D2R and Wnt5a has an important role in dopamine neuron development in association with EGFR and the ERK pathway.
authors: School of Life Sciences and Biotechnology, Korea University, Seoul, South Korea.
authors: Sehyoun
authors: S
authors: Yoon
authors: Mi-hyun
authors: MH
authors: Choi
authors: Min Seok
authors: MS
authors: Chang
authors: Ja-Hyun
authors: JH
authors: Baik
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018492:Dopamine Antagonists / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017434:Protein Structure, Tertiary; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: D018492:Dopamine Antagonists; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D013134:Spiperone; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases