A protein associated with toll-like receptor 4 (PRAT4A) regulates cell surface expression of TLR4.
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.
Wakabayashi
Yasutaka
Y
Division of Infectious Genetics, University of Tokyo, Japan.
Kobayashi
Makiko
M
Akashi-Takamura
Sachiko
S
Tanimura
Natsuko
N
Konno
Kazunori
K
Takahashi
Koichiro
K
Ishii
Takashi
T
Mizutani
Taketoshi
T
Iba
Hideo
H
Kouro
Taku
T
Takaki
Satoshi
S
Takatsu
Kiyoshi
K
Oda
Yoshiya
Y
Ishihama
Yasushi
Y
Saitoh
Shin-ichiroh
S
Miyake
Kensuke
K
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
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