Role of ErbB4 receptor in schizophrenia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: University of the Ryukyus
• Principal Investigator: Nakamine Sayomi 琉球大学, 医学(系)研究科(研究院), 准教授 (20381105)
• Co-Investigator(Kenkyū-buntansha): 鳥原 英嗣 琉球大学, 医学(系)研究科(研究院), 助教 (50757218) ; 山本 秀幸 琉球大学, 医学(系)研究科(研究院), 教授 (60191433)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: Pyk2 / Fyn / 神経細胞 / GT1-7細胞 / GnRH / PKD1

Outline of Final Research Achievements

The receptor for gonadotropin-releasing hormone (GnRH) belongs to the G-protein coupled receptors, and is highly expressed in hypothalamic neurons, as well as in anterior pituitary gonadotrophs. In our previous study, we found that GT1-7 cells expressed ErbB4 as well as EGFR, and GnRH treatment induced the cleavage of ErbB4 to suppress the function of ErbB4. In the present study, we found that ErbB4 was expressed in undifferentiated gonadotroph aT3-1 cells and GnRH induced the cleavage of ErbB4. We found that stimulation of the GnRH receptor activated protein kinase D1 (PKD1), and PKD1 was involved in the Fyn-mediated activation of proline-rich tyrosine kinase 2 (Pyk2) in GT1-7 cells. Pyk2 indicated that tyrosine 402 (Tyr402) was phosphorylated both by autophosphorylation and by Fyn, whereas Tyr579 was phosphorylated mainly by Fyn. Our present data may suggest that fully activated Pyk2 dissociates from Fyn after Fyn-mediated phosphorylation of Pyk2 at unknown sites.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

神経細胞における細胞内の情報伝達機構の解明は、統合失調症などの発症機序を解明する上で重要である。ゴナドトロピン受容体（GnRH）はGタンパク質共役型受容体の一つで、Gq/11タンパク質と共役している。今回、マウスの視床下部由来のGT1-7細胞で、GnRH受容体刺激によってCキナーゼによってPKD1が活性化され、Fynを介したチロシンキナーゼPyk2を活性化する詳細な機構が明らかになった。Gq/11タンパク質はアドレナリンのα1受容体など様々な受容体刺激で活性化されることが知られており、本研究はGq/11タンパク質が関与する細胞内情報伝達機構の解明に貢献すると考えられる。