Prof. Sabine Strahl Glycobiology
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.
The Strahl Lab - Glycobiology: Sweet Science
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 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.
[Figure: The biosynthetic pathway of O-mannosyl glycans in yeast (left) and mammals (right).]
Latest publications
Noor SI, Hoffmann M, Rinis N, Bartels MF, Winterhalter PR, Hoelscher C, Hennig R, Himmelreich N, Thiel C, Ruppert T, Rapp E, Strahl S. (2021) Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion. J Biol Chem. 296:100433. https://doi.org/10.1016/j.jbc.2021.100433
Chiapparino A, Grbavac A, Jonker HR, Hackmann Y, Mortensen S, Zatorska E, Schott A, Stier G, Saxena K, Wild K, Schwalbe H, Strahl S, Sinning I. (2020) Functional implications of MIR domains in protein O-mannosylation. Elife 9:e61189. https://doi.org/10.7554/eLife.61189
Funding
Sabine Strahl is spokesperson for GBM Studiengruppe Glykobiologie and DFG research unit FOR2509. She is member of "CellNetworks Exzellenzkluster", CRC1036 and graduate school HBIGS. Our work is funded by several public institutions, notably the “Deutsche Forschungsgemeinschaft” (DFG) and the Baden-Württemberg Ministry of Science, Research and the Arts (MWK).
