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Vortrag von David Teis

Vortragstitel: "Membrane quality control by the Dsc ubiquitin ligase complex"
Anlass: SFB - Seminar
Host: Florian Fröhlich
Beginn: 19.10.2023 - 16:15 Uhr
Ort: CellNanOs, 38/201

Über den Vortragenden: David Teis forscht im Fachgebiet Molekulare Zellbiologie an der Medizinischen Universität Innsbruck.

Inhalt des Vortrags: Controlling the accurate protein and lipid composition of membranes is vital for cells. We have shown earlier in S. cerevisiae, that endosome and Golgi associated degradation (EGAD) selectively ubiquitinates the integral membrane protein Orm2 for Cdc48 dependent membrane extraction and subsequent proteasomal degradation. The regulated degradation of Orm2 by EGAD functions to derepress sphingolipid biosynthesis. At the heart of EGAD operates the Dsc (defective for SREBP cleavage) complex, a multimeric transmembrane ubiquitin E3 ligase complex that consists of the ubiquitin E3 ligase Tul1, the rhomboid pseudo-protease Dsc2, the Cdc48 adaptor Ubx3 and the ubiquitin-like fold containing protein Dsc3.

Now we have addressed how the Dsc complex detects its substrates, using a combination of yeast genetics and quantitative proteomics. Our results revealed that the Dsc complex not only degraded Orm2, but was also essential for the selective degradation of several orphaned membrane proteins at the Golgi and on endosomes. The interaction with these substrates required the rhomboid pseudo-protease Dsc2, which might detect degrons in the transmembrane domains of different substrates. By degrading orphaned membrane proteins, the Dsc complex also helped to maintain proper membrane lipid composition. Hence, the Dsc complex mediates quality control processes that help to preserve cellular membranes.