Vinculin and Rab5 complex is required [correction of requited]for uptake of Staphylococcus aureus and interleukin-6 expression.
Vinculin, a 116-kDa membrane cytoskeletal protein, is an important molecule for cell adhesion; however, little is known about its other cellular functions. Here, we demonstrated that vinculin binds to Rab5 and is required for Staphylococcus aureus (S. aureus) uptake in cells. Viunculin directly bound to Rab5 and enhanced the activation of S. aureus uptake. Over-expression of active vinculin mutants enhanced S. aureus uptake, whereas over-expression of an inactive vinculin mutant decreased S. aureus uptake. Vinculin bound to Rab5 at the N-terminal region (1-258) of vinculin. Vinculin and Rab5 were involved in the S. aureus-induced phosphorylation of MAP kinases (p38, Erk, and JNK) and IL-6 expression. Finally, vinculin and Rab5 knockdown reduced infection of S. aureus, phosphorylation of MAPKs and IL-6 expression in murine lungs. Our results suggest that vinculin binds to Rab5 and that these two molecules cooperatively enhance bacterial infection and the inflammatory response.
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Makoto
M
Hagiwara
Department of Microbiology, Tokyo Dental College, Chiba, Japan.
Eitoyo
E
Kokubu
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Shinsuke
S
Sugiura
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Toshinori
T
Komatsu
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Hiroyuki
H
Tada
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Ryutaro
R
Isoda
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Naomi
N
Tanigawa
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Yoshiko
Y
Kato
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Naoyuki
N
Ishida
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Kaoru
K
Kobayashi
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Misako
M
Nakashima
Department of Microbiology, Tokyo Dental College, Chiba, Japan.
Kazuyuki
K
Ishihara
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Kenji
K
Matsushita
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004926:Escherichia coli; D005260:Female; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D015850:Interleukin-6 / Q000378:metabolism*; D007546:Isoquinolines / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013211:Staphylococcus aureus / Q000502:physiology*; D014168:Transferrin / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
D000418:Albumins; D015850:Interleukin-6; D007546:Isoquinolines; D014168:Transferrin; D016596:Vinculin; C017475:lucifer yellow; D020696:rab5 GTP-Binding Proteins