Involvement of Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) and Rac1 in the phagocytosis of amyloid-beta(1-42) in rat microglia.
Alzheimer's disease (AD) is characterized by the accumulation of extracellular amyloid-beta (A beta) fibrils with microglia. Recently, there has been great interest in the microglial phagocytosis of A beta, because the microglial pathway is considered to be one of the A beta clearance pathways in the brain parenchyma. However, the mechanism of microglial phagocytosis of A beta is not fully understood and, thus, was investigated in this study. At one minute after exposure to A beta(1-42) (A beta 42), A beta immunoreactivity was detected at the cell surface of microglia. After 1 h, marked immunoreactivity was observed in the cytosolic vesicles. At 12 h, delayed phagocytosis of fibrillar A beta 42 was also observed with the formation of a large phagocytic cup. The microglial cell shape rapidly changed to an ameboid form during the process of phagocytosis. Although neither neural Wiskott-Aldrich syndrome protein (N-WASP) nor WASP interacting SH3 protein (WISH) immunoreactivity was co-localized with filamentous actin (F-actin) distribution, both WASP family verprolin-homologous protein (WAVE) and Rac1 immunoreactivity was co-localized with F-actin in the lamellipodia of phogocytic microglia. These results suggest that WAVE and Rac1 participate in the phagocytosis of A beta 42 by microglia.
Kitamura
Yoshihisa
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Kyoto, Japan.
Shibagaki
Keiichi
K
Takata
Kazuyuki
K
Tsuchiya
Daiju
D
Taniguchi
Takashi
T
Gebicke-Haerter
Peter J
PJ
Miki
Hiroaki
H
Takenawa
Tadaomi
T
Shimohama
Shun
S
D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D008840:Microfilament Proteins / Q000032:analysis / Q000502:physiology*; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000502:physiology*; D014923:Wiskott-Aldrich Syndrome / Q000378:metabolism; D051300:Wiskott-Aldrich Syndrome Protein Family; D020830:rac1 GTP-Binding Protein / Q000032:analysis / Q000502:physiology*
D016229:Amyloid beta-Peptides; D008840:Microfilament Proteins; D010446:Peptide Fragments; D029701:Saccharomyces cerevisiae Proteins; C090350:VRP1 protein, S cerevisiae; D051300:Wiskott-Aldrich Syndrome Protein Family; C075222:amyloid beta-protein (1-42); D015638:Cytochalasin D; D020830:rac1 GTP-Binding Protein