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The role of NG2 glycoprotein in regulation of Rho/ROCK signaling
Kratochvílová, Magdalena ; Rösel, Daniel (advisor) ; Kuželová, Kateřina (referee)
NG2 is a transmembrane glycoprotein, which takes part in cellular processes such as adhesion, migration or invasivity, i.e., in processes important in tissue development but also in tumor and metastasis formation. Among other things, NG2 leads to an inhibition of neurite growth, and probably plays an important role in amoeboid type of cell invasion. These processes are in many respects similar. Both in inhibition of neurite growth and in mesenchymal-amoeboid transition occur morphological changes which lead to a loss of cell protrusions and a transition to a rounded shape. In both of these processes Rho/ROCK signaling also plays a crucial role. Connection between NG2 and the Rho/ROCK signaling pathway has been indicated in the process of inhibition of neurite growth. The mechanism of Rho/ROCK signaling regulation by NG2 glycoprotein is, however, still unknown. In this thesis is proposed a molecular mechanism of Rho/ROCK pathway activation by glycoprotein NG2 which relies on the NG2/MUPP1/Syx signaling complex where the scaffold protein MUPP1, bound to activated NG2, enables binding and activation of the Syx protein. Syx then as RhoGEF activates Rho/ROCK signaling, and the activated Rho/ROCK pathway leads to inhibition of neurite growth, increased cell contractility and traction forces. These processes are...
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The role of NG2 glycoprotein in the regulation of Rho/ROCK signaling.
Kratochvílová, Magdalena ; Rösel, Daniel (advisor) ; Libusová, Lenka (referee)
NG2 is a transmembrane glycoprotein mainly expressed in developing tissue, and often re-expressed in tumor cells. NG2 glycoprotein is an important regulator of cell migration and adhesion. Increased expression of NG2 enhances the metastatic potential of cancer cells. However, the molecular mechanisms of these processes are still not fully understood. An increasing number of evidences, in recent years, have shown that NG2 can be responsible for Rho/ROCK activation, which is essential for effective amoeboid invasiveness. In this thesis, we analysed the role of NG2 glycoprotein, especially the role of its PDZ- binding motif on amoeboid phenotype induction, and activation of Rho/ROCK signaling. Our results demonstrate the importance of the NG2 PDZ-binding motif on mesenchymal- amoeboid transition of cells in a 3D environment. Surprisingly, they show that the expression of both the NG2 cytoplasmatic domain and the truncated version, lacking the PDZ-binding motif, do not change the amount of Rho-GTP or the activation of the Rho/ROCK signaling pathway in 2D.
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The role of NG2 glycoprotein in regulation of Rho/ROCK signaling
Kratochvílová, Magdalena ; Rösel, Daniel (advisor) ; Kuželová, Kateřina (referee)
NG2 is a transmembrane glycoprotein, which takes part in cellular processes such as adhesion, migration or invasivity, i.e., in processes important in tissue development but also in tumor and metastasis formation. Among other things, NG2 leads to an inhibition of neurite growth, and probably plays an important role in amoeboid type of cell invasion. These processes are in many respects similar. Both in inhibition of neurite growth and in mesenchymal-amoeboid transition occur morphological changes which lead to a loss of cell protrusions and a transition to a rounded shape. In both of these processes Rho/ROCK signaling also plays a crucial role. Connection between NG2 and the Rho/ROCK signaling pathway has been indicated in the process of inhibition of neurite growth. The mechanism of Rho/ROCK signaling regulation by NG2 glycoprotein is, however, still unknown. In this thesis is proposed a molecular mechanism of Rho/ROCK pathway activation by glycoprotein NG2 which relies on the NG2/MUPP1/Syx signaling complex where the scaffold protein MUPP1, bound to activated NG2, enables binding and activation of the Syx protein. Syx then as RhoGEF activates Rho/ROCK signaling, and the activated Rho/ROCK pathway leads to inhibition of neurite growth, increased cell contractility and traction forces. These processes are...
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