Unravelling the molecular network of Lethal (2) giant discs (Lgd) in Drosophila melanogaster.
Final Report Abstract
The tumor-suppressor Lethal (2) giant discs (Lgd) of Drosophila is involved in the regulation of the ESCRT machinery, which is involved in the degradation of transmembrane proteins via formation of intraluminal vesicles (ILVs) at the maturing endosome (ME). The machinery consists of five core complexes, ESCRT0-III and Vps4. Lgd interacts with the core component of ESCRT-III, Shrub in Drosophila. In addition, two auxiliary complexes consisting of CHMP5/Vta and Did2/Ist1 respectively, are required for the full function of ESCRT-III. These complexes are poorly characterized in metazoans. In a genetic screen we identified the auxiliary ESCRT components Chmp5 and Ist1 as interactors of lgd. We have characterized the two genes in Drosophila. We found similar function as has been described in yeast before, namely that they are required for the full function of Vps4 and ESCRT- III. To our surprise we also found that the auxiliary ESCRTs are required in poikilothermic cells to neutralize the deleterious effects of Shrub accumulation on the limiting membrane of the ME in cold. This function is evolutionary conserved as we found that it holds true also in the unicellular eukaryotic pathogen U. maydis. In a second project we clarified the relationship between Lgd and the E3 Ligase Suppressor of deltex (Su(dx)), which has a qualitatively similar (albeit much weaker) phenotype than lgd mutants. The similarity raised the possibility that both genes act within the same pathway. By analyzing the phenotype of double mutants, we excluded this possibility.
Publications
- (2019). The auxiliary ESCRT complexes provide robustness to cold in poikilothermic organisms. Biol Open
Bäumers, M., Klose, S., Brüser, C., ,Haag, C., Hänsch, S., Pannen, H., Weidtkamp- Peters, S., Feldbrügge, M. and Klein, T.
(See online at https://doi.org/10.1242/bio.043422)
