Teis Lab

The function of cells depends on the integrity of their membranes and organelles. To maintain membrane integrity selective protein degradation machineries detect and selectively degrade mis-folded or orphaned proteins. By achieving this remarkable task, cellular quality-control networks maintain membrane protein homeostasis (proteostasis). Chronic defects membrane proteostasis causes loss of organelle integrity and cell injuries that are central to the pathophysiologies of prevalent human diseases, including cancer, autoimmunity, diabetes, obesity and neurodegeneration. How selective protein degradation pathways function is therefore a major question in biology.

To tackle this question, we aim to discover molecular mechanisms that connect cellular quality control processes to membrane lipid homeostasis in response to metabolic changes and cellular stress. To address these questions, my group combines genetic approaches in yeasts and human cells with quantitative biochemical and imaging approaches. Recently, we have (i) identified a novel membrane protein degradation pathway (EGAD) that selectively degrades membrane proteins in Golgi and endosomes to regulate sphingolipid homeostasis (Schmidt, O. EMBO J. 2019); (ii) characterised how metabolic signalling enlists adaptors for ubiquitin ligase complex to selectively degrade nutrient transporters (Ivashov V. et al., eLife 2020); (iii) discovered a role of the ESCRT machinery in regulating the interactions of chromosomes with the nuclear envelope (Pieper, G. et al Dev. Cell 2020) and (iv) described a function of the ESCRT machinery for maintaining the integrity of the plasma membrane (Schmidt, O. et al JBC. 2020).

Publications

https://pubmed.ncbi.nlm.nih.gov/?term=Teis+D&sort=date

The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi. Weyer Y, Schwabl SI, Tang X, Purwar A, Siegmann K, Ruepp A, Dunzendorfer-Matt T, Widerin MA, Niedrist V, Mutsters NJM, Tettamanti MG, Weys S, Sarg B, Kremser L, Liedl KR, Schmidt O, Teis D. Nat Commun. 2024 Oct 26;15(1):9257. doi: 10.1038/s41467-024-53676-6. PMID: 39461958 Free PMC article.

The structure of the Orm2-containing serine palmitoyltransferase complex reveals distinct inhibitory potentials of yeast Orm proteins. Körner C, Schäfer JH, Esch BM, Parey K, Walter S, Teis D, Januliene D, Schmidt O, Moeller A, Fröhlich F. Cell Rep. 2024 Aug 27;43(8):114627. doi: 10.1016/j.celrep.2024.114627. Epub 2024 Aug 20. PMID: 39167489 Free article.

Complementary α-arrestin-ubiquitin ligase complexes control nutrient transporter endocytosis in response to amino acids. Ivashov V, Zimmer J, Schwabl S, Kahlhofer J, Weys S, Gstir R, Jakschitz T, Kremser L, Bonn GK, Lindner H, Huber LA, Leon S, Schmidt O, Teis D. Elife. 2020 Aug 3;9:e58246. PMID:32744498 

ESCRT-III/Vps4 Controls Heterochromatin-Nuclear Envelope Attachments. Pieper GH, Sprenger S, Teis D, Oliferenko S. Dev Cell. 2020 Apr 6;53(1):27-41.e6.. PMID:32109380 

Endosome and Golgi-associated degradation (EGAD) of membrane proteins regulates sphingolipid metabolism. Schmidt O, Weyer Y, Baumann V, Widerin MA, Eising S, Angelova M, Schleiffer A, Kremser L, Lindner H, Peter M, Fröhlich F, Teis D. EMBO J. 2019 Aug 1;38(15):e101433. PMID:31368600 

TOR complex 2 (TORC2) signaling and the ESCRT machinery cooperate in the protection of plasma membrane integrity in yeast. Schmidt O, Weyer Y, Sprenger S, Widerin MA, Eising S, Baumann V, Angelova M, Loewith R, Stefan CJ, Hess MW, Fröhlich F, Teis D.J Biol Chem. 2020 Aug 21;295(34):12028-12044. PMID: 32611771

Collaborations

Robbie Loewith, University of Geneva, Geneva, CH

Snezhana Oliferenko, Francis Crick Institute, King’s College, UK

Benoit Kornmann, University of Oxford, Oxford, UK

Tomas Kirchhausen, Harvard Medical School, Cambridge, USA

Scott Emr, Cornell University, Ithaca, UK

Florian Fröhlich, Osnabrück University, Osnabrück, DE

Sebastian Leon, Université de Paris, Paris, F

Florian Wilfling, MPI Biophysik Frankfurt, DE

Funding

• FWF P 32161, P 30263 and P29583
• Coordination of FWF Doctoral Program DOC82: Cellular Basis of Diseases: Molecular Control of Metabolism and Inflammation

Univ.-Prof. Dr. David Teis
E-Mail: david.teis@i-med.ac.at
phone: +43 512 9003 70191