title: A molecule that is associated with Toll-like receptor 4 and regulates its cell surface expression.
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.
authors.affiliation: Division of Infectious Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Konno
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Akashi-Takamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishii
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kusumoto
authors.forename: Shin-ichiroh
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Yoshizawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D017124:Conserved Sequence; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D051218:Lymphocyte Antigen 96 / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C573502:CNPY4 protein, human; D002352:Carrier Proteins; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D018832:Molecular Chaperones; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C508076:TLR4-associated protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4