PMID- 17868382
OWN - NLM
STAT- MEDLINE
DCOM- 20080307
LR  - 20201209
IS  - 1462-5822 (Electronic)
IS  - 1462-5814 (Linking)
VI  - 10
IP  - 2
DP  - 2008 Feb
TI  - The major outer sheath protein of Treponema denticola selectively inhibits Rac1 
      activation in murine neutrophils.
PG  - 344-54
AB  - Treponema denticola major outer sheath protein (Msp) inhibits neutrophil 
      chemotaxis in vitro, but key regulatory mechanisms have not been identified. 
      Because the Rac small GTPases regulate directional migration in response to 
      chemoattractants, the objective was to analyse the effects of Msp on 
      formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated neutrophil polarization and 
      Rac activation in murine neutrophils. Msp pretreatment of neutrophils inhibited 
      both polarization and chemotactic migration in response to fMLP. Activation of 
      small GTPases was measured by p21 binding domain (PBD) pulldown assays, followed 
      by Western analysis, using monoclonal anti-Rac1, anti-Rac2, anti-cdc42 and 
      anti-RhoA antibodies. Enriched native Msp selectively inhibited fMLP-stimulated 
      Rac1 activation in a concentration-dependent manner, but did not affect Rac2, 
      cdc42 or RhoA activation. Murine neutrophils transfected with vectors expressing 
      fluorescent probes PAK-PBD-YFP and PH-AKT-RFP were used to determine the effects 
      of Msp on the localization of activated Rac and PI3 kinase products. Real-time 
      confocal images showed that Msp inhibited the polarized accumulation of activated 
      Rac and PI3-kinase products upon exposure to fMLP. The findings indicate that T. 
      denticola Msp inhibition of neutrophil polarity may be due to the selective 
      suppression of the Rac1 pathway.
FAU - Magalhaes, Marco A O
AU  - Magalhaes MA
AD  - CIHR Group in Matrix Dynamics and Dental Research Institute, University of 
      Toronto, Faculty of Dentistry, Toronto, Ontario, Canada.
FAU - Sun, Chun Xiang
AU  - Sun CX
FAU - Glogauer, Michael
AU  - Glogauer M
FAU - Ellen, Richard P
AU  - Ellen RP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070913
PL  - India
TA  - Cell Microbiol
JT  - Cellular microbiology
JID - 100883691
RN  - 0 (Bacterial Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Porins)
RN  - 0 (Rac1 protein, mouse)
RN  - 0 (major outer sheath protein, Treponema)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/metabolism/*physiology
MH  - Cell Polarity/drug effects
MH  - Chemotaxis/drug effects
MH  - Enzyme Activation
MH  - Mice
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neuropeptides/*metabolism
MH  - Neutrophils/drug effects/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Porins/metabolism/*physiology
MH  - Treponema denticola/*metabolism
MH  - rac GTP-Binding Proteins/*metabolism
MH  - rac1 GTP-Binding Protein
EDAT- 2007/09/18 09:00
MHDA- 2008/03/08 09:00
CRDT- 2007/09/18 09:00
PHST- 2007/09/18 09:00 [pubmed]
PHST- 2008/03/08 09:00 [medline]
PHST- 2007/09/18 09:00 [entrez]
AID - CMI1045 [pii]
AID - 10.1111/j.1462-5822.2007.01045.x [doi]
PST - ppublish
SO  - Cell Microbiol. 2008 Feb;10(2):344-54. doi: 10.1111/j.1462-5822.2007.01045.x. 
      Epub 2007 Sep 13.