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Vinculin and Rab5 Complex Is Requited for Uptake of Staphyrococcus aureus and Interleukin-6 Expression
Authors:Makoto Hagiwara  Eitoyo Kokubu  Shinsuke Sugiura  Toshinori Komatsu  Hiroyuki Tada  Ryutaro Isoda  Naomi Tanigawa  Yoshiko Kato  Naoyuki Ishida  Kaoru Kobayashi  Misako Nakashima  Kazuyuki Ishihara  Kenji Matsushita
Affiliation:1. Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.; 2. Department of Microbiology, Tokyo Dental College, Chiba, Japan.; University of California Merced, United States of America,
Abstract: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.
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