A molecule that is associated with Toll-like receptor 4 and regulates its cell surface expression

• Published in: Biochemical and biophysical research communications 2006-01, Vol.339 (4), p.1076-1082
• Main Authors: Konno, Kazunori, Wakabayashi, Yasutaka, Akashi-Takamura, Sachiko, Ishii, Takashi, Kobayashi, Makiko, Takahashi, Koichiro, Kusumoto, Yutaka, Saitoh, Shin-ichiroh, Yoshizawa, Yasuyuki, Miyake, Kensuke
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Binding Sites; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cell Membrane - metabolism; Cell surface molecules; Cells, Cultured; Conserved Sequence; Gene Expression Regulation - physiology; Humans; Innate immunity; Kidney - metabolism; Lipopolysaccharide; Lymphocyte Antigen 96 - metabolism; Molecular Chaperones - chemistry; Molecular Chaperones - metabolism; Molecular Sequence Data; Protein Binding; Sequence Homology, Amino Acid; Toll-Like Receptor 2 - metabolism; Toll-like receptor 4; Toll-Like Receptor 4 - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.11.123

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.