Division für Zellbiologie

David Teis MAIN

 

Membrane Traffic and Signaling

Associate Professor

David Teis

phone: +43/512/9003-70191
email: david.teis@i-med.ac.at
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Cell growth and survival requires the selective degradation of cellular components. Failure in cellular degradation systems result in severe defects in cell homeostasis which in turn can cause in a wide variety of diseases ranging from cancer to neurodegeneration. We are particularly interested in the molecular mechanisms required for the selective degradation of integral membrane proteins.
A key step for the selective degradation of membrane proteins occurs on endosomes, where the endosomal complexes required for transport (ESCRTs) bind to and sort ubiquitinated membrane proteins via the multivesicular body (MVB) pathway into the lumen of lysosomes for degradation (Figure 1).

 

Teis figure 1

Figure 1. Schematic representation of the MVB Pathway.

The ESCRT machinery is also somehow capable to remodeling and scission membrane thereby driving the biogenesis of intralumenal MVB vesicles (ILVs) (Figure 2A).
One key question in our lab is how the ESCRT machinery sculpts membranes and how ESCRT mediated membrane remodeling and scission is coordinated with cargo sorting (Figure 2B).

Teis figure 2

Figure 2. (A) 3D-Modeling of cryo-fixed cells. MVBs (yellow), Intralumenal MVB vesicles (ILVs) (red), vacuole (blue). (B) Model of ESCRT-III and Vps4 during ILV neck constriction.

Furthermore we would like to understand how the ESCRT dependent degradation of membrane proteins contributes to cell growth and survival, particularly given the key role of ESCRTs during developmental and disease.
To address these questions we use yeast as the best suited model system combining genetics with quantitative proteomics, biochemical methods and different imaging approaches (Figure 3A,B).

Teis figure 3

Figure 3. (A) Fluorescence microscopy of living yeast, vacuole (red), GFP-CPS (green). (B) Graphical representation of quantitive proteomics.

 

List of Publications

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