Molecular basis of basolateral CALHM channel sorting in epithelial cells

• Project/Area Number: 17K08543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Aichi Medical University
• Principal Investigator: Kashio Makiko 愛知医科大学, 医学部, 講師 (20631394)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 味細胞 / ATP / イオンチャネル / 生理学 / 味覚

Outline of Final Research Achievements

CALHM1/3 channel serves as a ATP-permeable ion channel which is necessary for neurotransmission from type 2 taste cells to taste nerve endings. CALHM1/3 channels selectively localize in basolateral membrane in epithelial cells including taste cells. This study has revealed the molecular mechanism enabling polarized transport of CALHM channels in epithelial cells which is embedding in the internal loop and C-terminal regions of CALHM1 and CALHM3. In addition, yeast two-hybrid study has identify a functionally unknown protein interacting with CALHM1 protein. These results suggest that CALHM1/3 channels are selectively localized to vicinity of taste nerve endings by multiple mechanisms.

Academic Significance and Societal Importance of the Research Achievements

CALHM1/3チャネルは甘味・うま味・苦味の受容を行う味細胞が神経へと情報伝達を行うために機能するイオンチャネルである。味の受容によって活性化したCALHM1/3チャネルがATPを遊離することで伝達が可能となっている。本研究では、味細胞においてCALHM1/3チャネルが神経と接する領域に限局的に配置されるメカニズムの解明を試みた。結果として、CALHM1/3分子内に細胞内での輸送を規定するシグナルが存在することを明らかにした。

Research Products

• [Journal Article] CALHM1/CALHM3 channel is intrinsically sorted to the basolateral membrane of epithelial cells including taste cells (2019)
  • Author(s): Kashio M, Wei-Qi G, Ohsaki Y, Kido MA, Taruno A
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 2681-2681
  • DOI: 10.1038/s41598-019-39593-5
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of TRPM2 and TRPM8 in temperature-dependent masking behavior (2019)
  • Author(s): Ota W, Nakane Y, Kashio M, Suzuki Y, Nakamura K, Mori Y, Tominaga M, Yoshimura T
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 3706-3706
  • DOI: 10.1038/s41598-019-40067-x
  • NAID: 120006817612
  • Peer Reviewed / Open Access
• [Journal Article] AAV-Mediated Gene Delivery to Taste Cells of the Tongue (2019)
  • Author(s): Taruno A and Kashio M
  • Journal Title: Methods in Molecular Biology Volume: 1950 Pages: 299-307
  • DOI: 10.1007/978-1-4939-9139-6_18
  • ISBN: 9781493991389, 9781493991396
  • Peer Reviewed / Open Access
• [Journal Article] HsTRPA of the Red Imported Fire Ant, Solenopsis invicta, Functions as a Nocisensor and Uncovers the Evolutionary Plasticity of HsTRPA Channels. (2018)
  • Author(s): Wang X, Li T2, Kashio M, Xu Y, Tominaga M, Kadowaki T.
  • Journal Title: eNeuro Volume: 5 Issue: 1 Pages: 0327-17
  • DOI: 10.1523/eneuro.0327-17.2018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The TRPM2 channel: A thermo-sensitive metabolic sensor (2017)
  • Author(s): Kashio Makiko、Tominaga Makoto
  • Journal Title: Channels (Austin) Volume: 11 Issue: 5 Pages: 426-433
  • DOI: 10.1080/19336950.2017.1344801
• [Journal Article] Subcellular localization of TRPM2 determines the fate of cancer cells, survival or apoptosis (2017)
  • Author(s): Makiko Kashio and Makoto Tominaga
  • Journal Title: Translational Cancer Research Volume: 6 Issue: S2 Pages: S409-S411
  • DOI: 10.21037/tcr.2017.03.09
  • Open Access
• [Presentation] Functional Coupling of Metabolic Sensors, TRPM2 and Sirtuin. (2020)
  • Author(s): Makiko Kashio, Makoto Tominaga, Satoru Masubuchi
  • Organizer: 第97回日本生理学会大会
• [Presentation] Functional coupling of metabolic sensors, TRPM2 and Sirtuin (2019)
  • Author(s): Makiko Kashio, Makoto Tominaga, Satoru Masubuchi
  • Organizer: FAOPS2019
  • Int'l Joint Research
• [Presentation] 感覚・免疫連関における体温センサーTRPM2の生理的意義 (2018)
  • Author(s): 加塩麻紀子
  • Organizer: 第2回感覚免疫研究会
  • Invited
• [Presentation] Transient receptor potential melastatin 2 (TRPM2), a thermo-sensitive metabolic sensor (2018)
  • Author(s): Makiko Kashio
  • Organizer: 第95回日本生理学会大会
  • Invited
• [Presentation] Transient receptor potential melastatin 2 (TRPM2), a thermo-sensitive metabolic sensor, regulates insulin secretion from the pancreatic β-cells (2018)
  • Author(s): Makiko Kashio and Makoto Tominaga
  • Organizer: 2018 Keystone Symposia Conference (J4: Bioenergetics and Metabolic Disease)
  • Int'l Joint Research
• [Book] Redox-Sensitive TRP Channels: TRPA1 and TRPM2 (2017)
  • Author(s): Makiko Kashio and Makoto Tominaga
  • Publisher: INTECHOPEN.COM
  • ISBN: 9789535133933