Slit3 regulates cell motility through Rac/Cdc42 activation in lipopolysaccharide-stimulated macrophages.
Three slit genes, slit1 to slit3, have been cloned to date. Slit1 and slit2 act as chemorepellent factors for axon guidance. Slit3 is involved in the formation of the diaphragm and kidney during embryogenesis. However, its molecular function remains unclear. We found that slit3 expression was induced by lipopolysaccharide (LPS)-stimulation in macrophages and that it was localized in the mitochondria and along the plasma membrane. Silencing of slit3 expression by RNA interference reduced cell motility and Rac/Cdc42 activation. These results suggest that slit3 functions as an intracellular signaling molecule for cell motility as part of the LPS-induced signaling cascade.
Tanno
Toshihiko
T
Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.
Fujiwara
Ayumi
A
Sakaguchi
Kunihiko
K
Tanaka
Katsuhiro
K
Takenaka
Shigeo
S
Tsuyama
Shingo
S
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D017931:DNA Primers; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; C432251:Slit3 protein, mouse; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins