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Description
| - Adenylate cyclase toxin (CyaA or ACT) is a key virulence factor of pathogenic Bordetellae. It penetrates phagocytes expressing the αMb2 integrin (CD11b/CD18, Mac-1 or CR3) and paralyzes their bactericidal capacities by uncontrolled conversion of ATP into a key signaling molecule, cAMP. Using pull-down activity assays and transfections with mutant Rho family GTPases, we show that cAMP signaling of CyaA causes transient and selective inactivation of RhoA in mouse macrophages in the absence of detectable activation of Rac1, Rac2, or RhoG. This CyaA/cAMP-induced drop of RhoA activity yielded dephosphorylation of the actin filament severing protein cofilin and massive actin cytoskeleton rearrangements, which were paralleled by rapidly manifested macrophage ruffling and a rapid and unexpected loss of macropinocytic fluid phase uptake. As shown in this study for the first time, CyaA/cAMP signaling further caused a rapid and near-complete block of complement-mediated phagocytosis
- Adenylate cyclase toxin (CyaA or ACT) is a key virulence factor of pathogenic Bordetellae. It penetrates phagocytes expressing the αMb2 integrin (CD11b/CD18, Mac-1 or CR3) and paralyzes their bactericidal capacities by uncontrolled conversion of ATP into a key signaling molecule, cAMP. Using pull-down activity assays and transfections with mutant Rho family GTPases, we show that cAMP signaling of CyaA causes transient and selective inactivation of RhoA in mouse macrophages in the absence of detectable activation of Rac1, Rac2, or RhoG. This CyaA/cAMP-induced drop of RhoA activity yielded dephosphorylation of the actin filament severing protein cofilin and massive actin cytoskeleton rearrangements, which were paralleled by rapidly manifested macrophage ruffling and a rapid and unexpected loss of macropinocytic fluid phase uptake. As shown in this study for the first time, CyaA/cAMP signaling further caused a rapid and near-complete block of complement-mediated phagocytosis (en)
- Adenylát cyklázový toxin (CyaA nebo ACT) je klíčový faktor virulence bakterie Bordetella pertussis, jež vyvolává onemocnění zvané černý kašel. Tento RTX (Repeats in ToXin family) protein o 1706 aminokyselinových zbytcích se specificky váže na myeloidními fagocyty, jako jsou neutrofily, makrofágy a dendritické buňky, exprimující receptor CyaA beta-2 integrin CD11b/CD18 (CR3, Mac-1). Po translokaci enzymatické adenylát cyklázové domény toxinu do cytosolu buněk, dochází k velmi efektivní přeměně ATP na cAMP a deregulaci buněčné cAMP signalizace. Ukazujeme, že CyaA aktivované cAMP signální dráhy vedou k inaktivaci malé GTPasy RhoA, a to má za následek prudkou reorganizaci aktinového cytoskeletu a vznik membránových protruzí, spolu s rychlou a efektivní inhibici komplementem-zprostředkované fagocytosy. Morfologické změny vyvolané CyaA jsou však zároveň doprovázeny inhibicí makropinocytosy, a tím představují zcela neobvyklý způsob rozvrácení buněčné signalizace bakteriálním toxinem (cs)
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Title
| - Adenylate Cyclase Toxin Subverts Phagocyte Function by RhoA Inhibition and Unproductive Ruffling
- Adenylate Cyclase Toxin Subverts Phagocyte Function by RhoA Inhibition and Unproductive Ruffling (en)
- Adenylát cyklázový toxin ovlivňuje fagocytární funkce inhibicí RhoA a neproduktivním rufflingem (cs)
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skos:prefLabel
| - Adenylate Cyclase Toxin Subverts Phagocyte Function by RhoA Inhibition and Unproductive Ruffling
- Adenylate Cyclase Toxin Subverts Phagocyte Function by RhoA Inhibition and Unproductive Ruffling (en)
- Adenylát cyklázový toxin ovlivňuje fagocytární funkce inhibicí RhoA a neproduktivním rufflingem (cs)
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skos:notation
| - RIV/61388971:_____/08:00313711!RIV09-AV0-61388971
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
| - P(1M0506), P(2B06161), P(GA310/08/0447), Z(AV0Z50200510)
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/61388971:_____/08:00313711
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - bordetella; adenylate cyclase toxin; rhoa (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...vavai/riv/projekt
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Benada, Oldřich
- Kamanová, Jana
- Šebo, Peter
- Kofroňová, Olga
- Mašín, Jiří
- Linhartová, Irena
- Vojtová, Jana
- Genth, H.
- Just, I.
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http://linked.open...ain/vavai/riv/wos
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http://linked.open...n/vavai/riv/zamer
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issn
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number of pages
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is http://linked.open...avai/riv/vysledek
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