Unc93B1 controls plasma membrane localization and signaling of TLR5

• Project/Area Number: 25860354
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: The University of Tokyo
• Principal Investigator: SHIBATA Takuma 東京大学, 医科学研究所, 助教 (30554505)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Unc93B1 / TLR5

Outline of Final Research Achievements

The proper trafficking and localization of Toll-like receptors (TLRs) are important for specific ligand recognition and efficient signal transduction. The nucleotide-sensing TLRs are believed to localize inside cells and signal from the endolysosomes. Trafficking of the nucleotide-sensing TLRs from the ER to the endolysosomes strictly depends on UNC93B1. Although UNC93B1 was considered to have no role for the cell surface-localized TLRs,we unexpectedly discovered that TLR5, a cell surface receptor for bacterial protein flagellin, also requires UNC93B1 for plasma membrane localization and signaling. TLR5 physically interacts with UNC93B1, and the cells from the 3d(H412R) or UNC93B1-deficient mice not only lack TLR5 at the plasma membrane but also fail to secret cytokines upon flagellin stimulation, demonstrating the essential role of UNC93B1 in TLR5 signaling. Our study reveals that the role of UNC93B1 is not limited to the TLRs signaling from the endolysosomes.

Research Products

• [Journal Article] UNC93B1 is essential for the plasma membrane localization and signaling of Toll-like receptor 5 (2014)
  • Author(s): Huh JW, Shibata T, Hwang M, Kwon EH, Jang MS, Fukui R, Kanno K, Jung DJ, Jang MH, Miyake K, and Kim YM
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 111 Issue: 19 Pages: 7072-7077
  • DOI: 10.1073/pnas.1322838111
  • Peer Reviewed
• [Presentation] Human TLR7/TLR8 are sensors for nucleoside derivatives (2014)
  • Author(s): 柴田 琢磨
  • Organizer: 第43回日本免疫学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Single Stranded RNA adjusts the TLR7/8 response to agonistic base analogues. (2013)
  • Author(s): 柴田 琢磨
  • Organizer: 第42回 日本免疫学会総会 学術集会
  • Place of Presentation: 千葉・幕張メッセ
• [Remarks] 東京大学医科学研究所・感染遺伝学分野
  • URL: http://www.ims.u-tokyo.ac.jp/kanseniden/index.html
• [Remarks] 東京大学医科学研究所・感染遺伝学分野
  • URL: http://www.ims.u-tokyo.ac.jp/kanseniden/index.html