Ruprecht-Karls-Universität Heidelberg
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Prof. Dr. Sabine Strahl

Prof. Dr. Sabine Strahl
Prof. Dr. Sabine Strahl
Im Neuenheimer Feld 360
69120 Heidelberg
Fon +49 6221 54-6286
Fax +49 6221 54-5859
sabine.strahl AET

Office hours Monday 1:15- 2:00 pm




The Strahl Lab - Glycobiology: Sweet Science

Glycosylation is one of the most abundant and complex protein modifications known. In many biological systems more than half of all proteins are glycosylated and glycan chains are highly crucial for a wide range of biological processes. Our laboratory is interested in various aspects of glycobiology in eukaryotic organisms with a main focus on O-mannosylation, an evolutionarily conserved, essential protein modification with immense impact on a variety of cellular processes in humans. Defective O-mannosylation results in severe muscular dystrophy and malfunctions of the brain and the eyes. Having identified the first protein O-mannosyltransferase PMT1 in the model organism yeast, our work has substantially contributed to the understanding of protein O-mannosylation in eukaryotes. The laboratory continues to work on the molecular organization of the O-mannosylation machinery in the endoplasmic reticulum (ER) and the role of O-mannosyl glycans for growth and development of fungi and mammals.

Protein O-Mannosylation, an essential modification that is conserved from yeast to human

O-mannosyl glycans are short linear oligo-saccharides linked via an alpha-glycosidically-bound mannose to Ser and Thr residues. Biosynthesis is initiated at the endoplasmic reticulum (ER) by the transfer of mannose from dolichyl phosphate-activated mannose to Ser or Thr residues of proteins that are entering the secretory pathway. Further chain elongation takes place in the Golgi apparatus using nucleotide-activated sugars as donors.

The initial mannosyltransfer reaction is catalyzed by an essential family of Dol-P-mannose: protein O-mannosyl-transferases (PMTs) that is evolutionarily conserved from yeast to humans. Focusing on PMTs we aim to understand how the ER O-mannosylation machinery works. Further, we analyze the occurrence and functions of O-mannosyl glycans in the eukaryotic model system baker's yeast and in mammals.


The biosynthetic pathway of O-mannosyl glycans in yeast (left) and mammals (right).

Please click on image to enlarge


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Latest News


Latest Publications

Castells-Ballester J, Ewa Zatorska E, Meurer M, Neubert P, Metschies A, Knop M and Strahl S. (2018). Monitoring Protein Dynamics in Protein-Mannosyltransferase Mutants In Vivo by Tandem Fluorescent Protein Timers. Molecules. 23(10), 2622;

For proteins entering the secretory pathway, a major factor contributing to maturation and homeostasis is glycosylation. One relevant type of protein glycosylation is O-mannosylation, which is essential and evolutionarily-conserved in fungi, animals, and humans. Our recent proteome-wide study in the eukaryotic model organism Saccharomyces cerevisiae revealed that more than 26% of all proteins entering the secretory pathway receive O-mannosyl glycans. In a first attempt to understand the impact of O-mannosylation on these proteins, we took advantage of a tandem fluorescent timer (tFT) reporter to monitor different aspects of protein dynamics. We analyzed tFT-reporter fusions of 137 unique O-mannosylated proteins, mainly of the secretory pathway and the plasma membrane, in mutants lacking the major protein O-mannosyltransferases Pmt1, Pmt2, or Pmt4. In these three pmtΔ mutants, a total of 39 individual proteins were clearly affected, and Pmt-specific substrate proteins could be identified. We observed that O-mannosylation may cause both enhanced and diminished protein abundance and/or stability when compromised, and verified our findings on the examples of Axl2-tFT and Kre6-tFT fusion proteins. The identified target proteins are a valuable resource towards unraveling the multiple functions of O-mannosylation at the molecular level.



Zatorska E, Gal L, Schmitt J, Bausewein D, Schuldiner M and Strahl S. (2018). Cellular Consequences of Diminished Protein O-Mannosyltransferase Activity in Baker’s Yeast. Int. J. Mol. Sci. 18, 1226; doi:10.3390/ijms18061226  

O-Mannosylation is a type of protein glycosylation initiated in the endoplasmic reticulum (ER) by the protein O-mannosyltransferase (PMT) family. Despite the vital role of O-mannosylation, its molecular functions and regulation are not fully characterized. To further explore the cellular impact of protein O-mannosylation, we performed a genome-wide screen to identify Saccharomyces cerevisiae mutants with increased sensitivity towards the PMT-specific inhibitor compound R3A-5a. We identified the cell wall and the ER as the cell compartments affected most upon PMT inhibition. Especially mutants with defects in N-glycosylation, biosynthesis of glycosylphosphatidylinositol-anchored proteins and cell wall -1,6-glucan showed impaired growth when O-mannosylation became limiting. Signaling pathways that counteract cell wall defects and unbalanced ER homeostasis, namely the cell wall integrity pathway and the unfolded protein response, were highly crucial for the cell growth. Moreover, among the most affected mutants, we identified Ost3, one of two homologous subunits of the oligosaccharyltransferase complexes involved in N-glycosylation, suggesting a functional link between the two pathways. Indeed, we identified Pmt2 as a substrate for Ost3 suggesting that the reduced function of Pmt2 in the absence of N-glycosylation promoted sensitivity to the drug. Interestingly, even though S. cerevisiae Pmt1 and Pmt2 proteins are highly similar on the sequence, as well as the structural level and act as a complex, we identified only Pmt2, but not Pmt1, as an Ost3-specific substrate protein.


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