TY - JOUR
T1 - Modulation of Brucella-induced macropinocytosis by lipid rafts mediates intracellular replication
AU - Watarai, Masahisa
AU - Makino, Sou Ichi
AU - Fujii, Yoshio
AU - Okamoto, Keinosuke
AU - Shirahata, Toshikazu
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - Intracellular replication of Brucella requires the VirB complex, which is highly similar to conjugative DNA transfer systems. In this study, we show that Brucella internalizes into macrophages by swimming on the cell surface with generalized membrane ruffling for several minutes, after which the bacteria are enclosed by macropinosomes. Lipid raft-associated molecules such as glycosylphosphatidylinositol (GPI)-anchored proteins, GM1 gangliosides and cholesterol were selectively incorporated into macropinosomes containing Brucella. In contrast, lysosomal glycoprotein LAMP-1 and host cell transmembrane protein CD44 were excluded from the macropinosomes. Removing GPI-anchored proteins from the macrophage surface and cholesterol sequestration markedly inhibited the VirB-dependent macropinocytosis and intracellular replication. Our results suggest that the entry route of Brucella into the macrophage determines the intracellular fate of the bacteria that is modulated by lipid raft microdomains.
AB - Intracellular replication of Brucella requires the VirB complex, which is highly similar to conjugative DNA transfer systems. In this study, we show that Brucella internalizes into macrophages by swimming on the cell surface with generalized membrane ruffling for several minutes, after which the bacteria are enclosed by macropinosomes. Lipid raft-associated molecules such as glycosylphosphatidylinositol (GPI)-anchored proteins, GM1 gangliosides and cholesterol were selectively incorporated into macropinosomes containing Brucella. In contrast, lysosomal glycoprotein LAMP-1 and host cell transmembrane protein CD44 were excluded from the macropinosomes. Removing GPI-anchored proteins from the macrophage surface and cholesterol sequestration markedly inhibited the VirB-dependent macropinocytosis and intracellular replication. Our results suggest that the entry route of Brucella into the macrophage determines the intracellular fate of the bacteria that is modulated by lipid raft microdomains.
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U2 - 10.1046/j.1462-5822.2002.00195.x
DO - 10.1046/j.1462-5822.2002.00195.x
M3 - Article
C2 - 12067319
AN - SCOPUS:0036307071
VL - 4
SP - 341
EP - 355
JO - Cellular Microbiology
JF - Cellular Microbiology
SN - 1462-5814
IS - 6
ER -