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In vitro models for studying Syncytin-1-induced fusion of trophoblast cells
Jech, Lukáš ; Trejbalová, Kateřina (advisor) ; Zíková, Martina (referee)
Trophoblast cell fusion is essential for human placenta development. Apart from initiating blastocyst implantation, syncytialization is critical for optimal nutrient and gas exchange between mother and fo- etus. Multicellular syncytia called syncytiotrophoblast covers the surface of the branched structure of chorionic villi, which is in direct contact with maternal blood. Impairment of the syncytialization process leads to insufficient fetal nutrition and severe pregnancy complications. Syncytia formation is induced by the interaction of the surface glycoprotein of retrovital origin, Syncytin-1, with its receptor. Despite the significance of these processes, the details of cell fusion and trophoblast differentiation remain unk- nown. Furthermore, because of its uniqueness, the human placenta cannot be covered by animal models. As a result, research into human placental development, especially Syncytin-1-induced trophoblast cell fusion, is limited to in vitro trophoblast models. These models include primary trophoblast cell cultures and trophoblast cell lines, which can be obtained by immortalizing cell cultures or extracted from trophoblast tumours. Dedifferentiated trophoblast stem cell cultures were also established. The most recent approach, however, involves the direct reprogramming of dermal...
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Interaction of transmembrane proteins ASCT1 and ASCT2 with retroviral envelope glycoproteins
Trávníček, Martin ; Trejbalová, Kateřina (advisor) ; Mělková, Zora (referee)
Transmembrane proteins ASCT1 and ASCT2 are ubiquitous neutral amino acid transporters. Apart from their transporter function in metabolically active cells, they also serve as receptors for a wide group of retroviruses. All retroviruses recognizing the transmembrane receptor ASCT2/ASCT1 share a similar env gene, encoding the envelope glycoprotein. Syncytin-1 is the envelope glycoprotein, encoded by human endogenous retrovirus type W, produced in placental cytotrophoblasts of primates, including human. Interaction of receptor binding domain of Syncytin-1 and specific extracellular region of ASCT2 is responsible for fusion of neighbouring cells and formation of multinucleated syncytiotrophoblast. The importance of syncytiotrophoblast lies in higher efficiency of feto-maternal exchange of nutrients and simultaneously in modulation of immune response of mother towards fetus. Defect in syncytiotrophoblast differentiation often leads to complications during pregnancy and impairs the proper development of embryo. Characterization of protein domains responsible for the interaction between Syncytin-1 and its receptors is important to uncover genetic causes of these pathologies. Furthermore, understanding the interaction helps us to clarify the mechanism of cell entry and explains the molecular basis of host...
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