The physiological role of TASK channel-induced adrenaline secretion

• Project/Area Number: 18K06865
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Yokohama College of Pharmacy (2020); University of Occupational and Environmental Health, Japan (2018-2019)
• Principal Investigator: Matsuoka Hidetada 横浜薬科大学, 薬学部, 准教授 (90374991)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: TASKチャネル / TASK1チャネル / p11タンパク質 / PC12細胞 / TASK1 channel / endocytosis / PC12 cell / p11 / TASK channel

Outline of Final Research Achievements

I investigated the function and physiological role of TASK1 channels in endocrine cells. Pharmacological and molecular biological analyses showed that TASK1 channels are regulated by the clathrin-dependent endocytosis in NGF- and muscarine-stimulated adrenal medullary and PC12 cells. Furthermore, it showed that muscarine-induced endocytosis of TASK1 channels is regulated through PKC-Pyk2-Src pathway in PC12 cells. Additionally, TASK1 channels were localized at plasma membrane in PC12 cells is due to a lack of p11 protein. On the other hand, the treatment with NGF of PC12 cells was induced the expression of p11 proteins and resulted in a change in membrane localization of TASK1 channels. These results indicate that TASK1 channels were translocated and localized to plasma membrane by dissociating from p11 proteins.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、TASK1チャネルの機能調節機構を明らかにした。ムスカリン受容体によるKチャネルの抑制は、多くのチャネルが、gatingの変化によって制御されていることが知られている。今回申請者は、Kチャネルの1つであるTASK1チャネルの抑制には、gatingの変化だけでなくエンドサイトーシスが関与することを世界で初めて明らかにした。本研究成果は、TASKチャネルファミリーの機能制御機構を明らかにするとともに、未解明の多くのKチャネルの機能制御機構の解明を推進するものと期待され、学術的意義は高い。

Research Products

• [Journal Article] Mechanisms for establishment of GABA signaling in adrenal medullary chromaffin cells (2021)
  • Author(s): Harada K, Matsuoka M, Toyohira Y, Inoue M
  • Journal Title: J Neurochem. Volume: - Issue: 2 Pages: 153-168
  • DOI: 10.1111/jnc.15345
  • Peer Reviewed
• [Journal Article] Expression of p11 and heteromeric TASK channels in rat carotid body glomus cells and nerve growth factor differentiated PC12 cells (2020)
  • Author(s): Matsuoka H, Pokorski M, Harada K, Yoshimura R, Inoue M
  • Journal Title: J Histochem Cytochem. Volume: 68 Issue: 10 Pages: 679-690
  • DOI: 10.1369/0022155420955246
  • Peer Reviewed
• [Journal Article] TASK channels: channelopathies, trafficking, and receptor-mediated inhibition. (2020)
  • Author(s): Inoue, M, Matsuoka, H., Harada, K., Mugishima, G., Kameyama, M.
  • Journal Title: European Journal of Physiology Volume: 472 Issue: 7 Pages: 911-922
  • DOI: 10.1007/s00424-020-02403-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vexin is upregulated in cerebral cortical neurons by brain‐derived neurotrophic factor (2020)
  • Author(s): Hisatsugu Koshimizu, Shingo Suzuki, Anna Kawai, Ryuichiro Miura, Ken‐ichi Ohta, Takanori Miki, Naoki Adachi, Hidetada Matsuoka
  • Journal Title: Neuropsychopharmacol Rep. Volume: 40 Issue: 3 Pages: 275-280
  • DOI: 10.1002/npr2.12119
  • Peer Reviewed / Open Access
• [Journal Article] Mechanisms for pituitary adenylate cyclase-activating polypeptide-induced increase in excitability in guinea-pig and mouse adrenal medullary cells. (2020)
  • Author(s): Inoue M, Harada K, Matsuoka H.
  • Journal Title: Eur J Pharmacol Volume: 5;872 Pages: 172956-172956
  • DOI: 10.1016/j.ejphar.2020.172956
  • Peer Reviewed
• [Journal Article] Muscarinic receptor stimulation induces TASK1 channel endocytosis through a PKC-Pyk2-Src pathway in PC12 cells. (2020)
  • Author(s): Matsuoka H, Harada K, Mashima K, Inoue M.
  • Journal Title: Cell Signal. Volume: 65 Pages: 109434-109434
  • DOI: 10.1016/j.cellsig.2019.109434
  • Peer Reviewed
• [Journal Article] STIM1-dependent membrane insertion of heteromeric TRPC1-TRPC4 channels in response to muscarinic receptor stimulation. (2019)
  • Author(s): Harada K, Matsuoka H, Inoue M.
  • Journal Title: J Cell Sci. Volume: 31;132(11). Issue: 11 Pages: 229389-229389
  • DOI: 10.1242/jcs.227389
  • Peer Reviewed
• [Journal Article] Lack of p11 expression facilitates acidity-sensing function of TASK1 channels in mouse adrenal medullary cells (2019)
  • Author(s): Inoue Masumi、Matsuoka Hidetada、Lesage Florian、Harada Keita
  • Journal Title: The FASEB Journal Volume: 33 Issue: 1 Pages: 455-468
  • DOI: 10.1096/fj.201800407rr
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Differences among muscarinic agonists in M1 receptor-mediated nonselective cation channel activation and TASK1 channel inhibition in adrenal medullary cells. (2019)
  • Author(s): Inoue M, Harada K, Matsui M, Matsuoka H.
  • Journal Title: Eur J Pharmacol. Volume: 15;843 Pages: 104-112
  • DOI: 10.1016/j.ejphar.2018.11.021
  • Peer Reviewed
• [Journal Article] Expression and regulation of M-type K+ channel in PC12 cells and rat adrenal medullary cells. (2018)
  • Author(s): Harada K, Matsuoka H, Inoue M.
  • Journal Title: Cell Tissue Res. Volume: 372(3) Issue: 3 Pages: 457-468
  • DOI: 10.1007/s00441-018-2824-z
  • Peer Reviewed
• [Presentation] 副腎におけるアロプレグナノロン産生細胞の同定、および副腎髄質細胞におけるGABAシグナル機構の成長における変化 (2020)
  • Author(s): Keita Harada, Hidetada Matsuoka, Yuchio Yanagawa, Masumi Inoue
  • Organizer: 第97回日本生理学会大会
• [Presentation] The roles of p11 for the localization and heteromeric channel formation of TASK1 and TASK3 isoforms (2019)
  • Author(s): Matsuoka H, Harada K, Inoe M
  • Organizer: 9th Federation of Asian and Oceanian Physiological Societies Congress (FAOPS2019)
  • Int'l Joint Research
• [Presentation] Molecular mechanism for muscarinic receptor-mediated endocytosis of TASK1 channels in rat adrenal medullary cells (2018)
  • Author(s): Matsuoka H and Inoue M
  • Organizer: 第95回日本生理学会大会