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Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
A molecule that is associated with Toll-like receptor 4 and regulates its cell surface expression
Kazunori Konno1, Yasutaka Wakabayashi, Sachiko Akashi-Takamura
1Division of Infectious Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Abstract:
Toll-like receptors (TLRs) recognize microbial products and induce immune responses. Their subcellular distribution is believed to be optimized for their pathogen recognition. Little is known, however, about molecular mechanisms regulating the subcellular distribution of TLR. Lipopolysaccharide, a principal membrane component of the Gram-negative bacteria, is recognized by the receptor complex consisting of Toll-like receptor 4 (TLR4) and MD-2. We here show that a novel molecule, a PRotein Associated with Tlr4 (PRAT4B), regulates cell surface expression of TLR4. PRAT4B has a signal peptide followed by a mature peptide. PRAT4B is associated with the hypoglycosylated, immature form of TLR4 but not with MD-2 or TLR2. Downregulation of PRAT4B mRNA with small interfering RNA decreased cell surface TLR4 on HEK293 cells. These results suggest a novel mechanism regulating the subcellular distribution of TLR4.
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