Die Funktion der ESCRT Maschinerie bei der Aufrechterhaltung der Septate Junctions von Epithelien in Drosophila
Entwicklungsbiologie
Zusammenfassung der Projektergebnisse
The work performed in the frame of this identified a novel rather complicated pathway required to transport newly synthesised septate junction components to the apical SJ during maintenance of the epithelial polarity. It further identified several signalling pathways that are activated upon depletion of ESCRT function, among the so far not previously monitored mTOR pathway. It also hints to the mechanism of activation of the JunK-pathway by Crbs and Grnd. Moreover, it showed that EMT factors are activated and highlight more similarity between the neoplastic transformation in Drosophila and human cancer. However, although it is clear that the Notch pathway is one of the first signalling-pathway activated, a clear sequence of activation of the identified pathways has not achieved and is an aim for the near future in the lab. Moreover, we will address the function of the EMT factors and the question how the JunK contributes to the observed neoplastic transformation of the disc epithelium. It is worth mention that in the most established cancer models combination of loss and gain of function of genes are used to induce neoplastic transformation, e. g. the combination scribble mutant with over-expression of activated Ras (RasV12). In contrast the loss of a single ESCRT gene is sufficient to induce full transformation.
Projektbezogene Publikationen (Auswahl)
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Lethal (2) giant discs (Lgd)/CC2D1 is required for the full activity of the ESCRT machinery. BMC Biology, 18(1).
Baeumers, Miriam; Ruhnau, Kristina; Breuer, Thomas; Pannen, Hendrik; Goerlich, Bastian; Kniebel, Anna; Haensch, Sebastian; Weidtkamp-Peters, Stefanie; Schmitt, Lutz & Klein, Thomas
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The ESCRT machinery regulates retromer-dependent transcytosis of septate junction components in Drosophila. eLife, 9.
Pannen, Hendrik; Rapp, Tim & Klein, Thomas
