The Teis Laboratory: Membrane Proteostasis and Signalling

Twitter handle: @teislab

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 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

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

• 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

Team