|
|
The regulation of cofilin by the ERK signaling cascade
Rasl, Jan ; Vomastek, Tomáš (advisor) ; Gahura, Ondřej (referee)
Cofilin is small ubiquitous actin binding protein, which is required for polymerization and depolymerization of actin fibers. Cofilin is involved in numerous cellular processes where the remodeling of actin cytoskeleton is required, such as cell division and cell migration. In order to precisely and dynamically regulate the cofilin activity, cells utilize large network of interconnected signaling pathways. One of these signaling pathways is the MAP-kinase cascade ERK (extracellular signal-regulated kinase), although the molecular mechanisms by which ERK regulates cofilin activity are not fully understood. Much evidence suggests that ERK controls the cofilin activity mainly through the regulation of Rho family of small GTPases. The ERK signaling cascade can modulates the Rho GTPase pathway signaling components, such as GAPs (GTPase activating proteins), GEFs (guanine nucleotide exchange factors) or Rho GTPases effectors. The ERK signaling cascade utilizes two different mechanisms for the regulation of Rho GTPases signaling pathways. The first mechanism is on transcriptional and translational level, where ERK regulates the transcription and subsequently translation of key regulatory proteins. Second mechanism, which is far more dynamic, occurs at the level of posttranslational modification,...
|
|
| |
|
|
The Role of Lipid Rafts in Translocation of the Adenylate Cyclase Toxin of B. pertussis across Cytoplasmatic Membrane
Chvojková, Věra ; Gahura, Ondřej (referee) ; Šebo, Peter (advisor)
The bacterium Bordetella pertussis is the causative agent of pertussis or whooping cough. The main virulent factor of this gram-negative bacterium is adenylate cyclase toxin, a member of the RTX protein family. After secretion, the toxin binds to CD11b/CD18 integrin receptor of myeloid phagocytic cells and consequently translocates its adenylate cyclase enzyme (AC) into the cytosol of the host cells. In the cytosol, the AC is activated by calmodulin, followed by rapid conversion of ATP into the signaling molecule cAMP, resulting in paralysis of bactericidal functions of phagocytic cells. Recently it was shown that translocation of the catalytic AC domain into the cytosol proceeds in two steps. After binding of CyaA to the receptor, the influx of calcium ions into the cell occurs. High local concentration of calcium induces the translocation of the CyaA- CD11b/CD18 complex into the lipid raft, where the translocation of adenylate cyclase enzyme into cytosol occurs. This work is aiming on the description of the new established paradigm dealing with membrane translocation of RTX toxins.
|
|
| |
guest ::
