| Budget Amount *help |
¥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)
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| 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.
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