GTPase activating protein function of p85 facilitates uptake and recycling of the beta1 integrin.

Biochemical and Biophysical Research Communications
Traci E StankiewiczSusan A McDowell

Abstract

Beta1-containing adhesions at the plasma membrane function as dynamic complexes to provide bidirectional communication between the cell and its environment, yet commonly are used by pathogens to gain host cell entry. Recently, the cholesterol-lowering drug simvastatin was found to inhibit host invasion through beta1-containing adhesion complexes. To better understand the regulatory mechanisms controlling adhesion formation and uptake and the use of these complexes by Staphylococcus aureus, the primary etiologic agent in sepsis, bacteremia and endocarditis, we investigated the mechanism of inhibition by simvastatin. In response to simvastatin, adhesion complexes diminished as well as beta1 trafficking to the plasma membrane required to initiate adhesion formation. Simvastatin stimulated CDC42 activation and coupling to p85, a small-guanosine triphosphatase (GTPase) activating protein (GAP), yet sequestered CDC42 coupled to p85 within the cytosol. Loss of p85 GAP activity through use of genetic strategies decreased host cell invasion as well as beta1 trafficking. From these findings, we propose a mechanism whereby p85 GAP activity localized within membrane compartments facilitates beta1 trafficking. By sequestering p85 within the...Continue Reading

References

Nov 1, 1995·The Journal of Cell Biology·S MiyamotoK M Yamada
Apr 13, 2000·Biochimica Et Biophysica Acta·M Sinensky
Sep 21, 2004·The Journal of Biological Chemistry·M Dean ChamberlainDeborah H Anderson
Nov 9, 2004·Atherosclerosis. Supplements·Akira Endo
Apr 24, 2007·The Lancet Infectious Diseases·Marius TerblancheDaniel G Hackam
Apr 5, 2008·The Journal of Pharmacology and Experimental Therapeutics·Mary P HornSusan A McDowell
Feb 12, 2009·Trends in Microbiology·Christian Garzoni, William L Kelley
Mar 14, 2009·Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine·Michael W DonninoNathan I Shapiro
May 30, 2009·Pharmacotherapy·Paul P DobeshKeith M Olsen

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