Dokument

Zusammenfassung:
Plasmodium falciparum exportiert Proteine in den Wirtserythrozyt, die die Wirtszelle morphologisch modifizieren. Eine wichtige Konsequenz dieser morphologischen Veränderung der Wirtszelle ist die Eigenschaft der infizierten Zellen an Rezeptoren im Endothel der Blutgefässe zu binden. Diese adhäsiven Eigenschaften sind verantwortlich für die klinischen Symptome der Malaria Krankheit. Die exportierten Proteine müssen den sekretorischen Weg des Parasiten und die den Parasiten umschließende Parasitophore Vakuole durchqueren, bevor sie das Zytosol oder die Plasmamembran der Wirtszelle erreichen. Der Fokus dieser Arbeit liegt auf dem Eintritt von Proteinen in den sekretorischen Weg des Parasiten, dabei insbesondere auf der Erkennung untypisch verlängerter Signalsequenzen. In dieser Arbeit wurde die Funktion der untypischen Signalsequenz des Glykophorin bindenden Proteins 130 (GBP 130) untersucht. Diese Signalsequenz besitzt eine ungewöhnliche Nterminale Verlängerung von 47 Aminosäuren (AS). Der Effekt dieser N-terminalen Verlängerung von GBP 130 auf die Proteinsortierung in Plasmodium wurde im Detail untersucht. Dabei konnte gezeigt werden, dass die N-terminale Verlängerung keinerlei Einfluss auf die Endbestimmung des Proteins hat und dass die Nterminale Verlängerung kompatibel mit dem Transport löslicher Proteine ist. Zudem wurde gezeigt, dass die verlängerte Signalsequenz von GBP 130 kein für Plasmodium spezifisches ER-Erkennungssignal ist, da sie auch vom sekretorischen Weg von Humanzellen erkannt wird.

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