title: A protein associated with toll-like receptor 4 (PRAT4A) regulates cell surface expression of TLR4.
abstract: TLRs recognize microbial products. Their subcellular distribution is optimized for microbial recognition. Little is known, however, about mechanisms regulating the subcellular distribution of TLRs. LPS is recognized by the receptor complex consisting of TLR4 and MD-2. Although MD-2, a coreceptor for TLR4, enhances cell surface expression of TLR4, an additional mechanism regulating TLR4 distribution has been suggested. We show here that PRAT4A, a novel protein associated with TLR4, regulates cell surface expression of TLR4. PRAT4A is associated with the immature form of TLR4 but not with MD-2 or TLR2. PRAT4A knockdown abolished LPS responsiveness in a cell line expressing TLR4/MD-2, probably due to the lack of cell surface TLR4. PRAT4A knockdown down-regulated cell surface TLR4/MD-2 on dendritic cells. These results demonstrate a novel mechanism regulating TLR4/MD-2 expression on the cell surface.
authors.affiliation: Division of Infectious Genetics, University of Tokyo, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Akashi-Takamura
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tanimura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Konno
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishii
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Mizutani
authors.forename: Hideo
authors.initials: H
authors.lastname: Iba
authors.forename: Taku
authors.initials: T
authors.lastname: Kouro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takaki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Oda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.forename: Shin-ichiroh
authors.initials: S
authors.lastname: Saitoh
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D051218:Lymphocyte Antigen 96 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
chemical_list: C000632162:CNPY3 protein, human; D002352:Carrier Proteins; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; C508076:TLR4-associated protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4