Prof. Dr. Sabine Strahl
 | Prof. Dr. Sabine Strahl
Im Neuenheimer Feld 360 69120 Heidelberg Fon +49 6221 54-6286 Fax +49 6221 54-5859 ed.grebledieh-inu.soc TEA lharts.enibas |
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. 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 ER and the role of O-mannosyl glycans for growth and developement.
Protein O-Mannosylation, an essential modification that is conserved from yeast to human
O-mannosyl glycans are short linear oligosaccharides 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-mannosyltransferases (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 eukaryotic model systems.
The principles of O-mannosylation and its interplay with N-glycosylation in baker´s yeast.
Protein translocation in the endoplasmic reticulum (ER) and protein glycosylation are intimately connected, fundamental processes essential for the normal functioning of eukaryotic cells. Nascent polypeptide chains of secretory and membrane proteins are N-glycosylated and O-mannosylated while they are translocated across the ER membrane. The translocation and concurrent N-glycosylation of these proteins take place on a large molecular machine, the translocon complex (TC), which is associated with membrane-bound polysomes. We recently demonstrated that in Saccharomyces cerevisiae Pmt1-Pmt2 complexes associate with the Sec61 translocon as well as oligosaccharyltransferase (Loibl et al. (2014) J Biol Chem. 289). We established a cell free translation/translocation/glycosylation system which now allows us to unravel the molecular basis of coupling protein translocation and N-glycosylation with protein O-mannosylation.
People involved: Daniela Bausewein, Ewa Zatorska
The role of protein O-mannosylation in the unfolded protein response SFB1036
In all eukaryotes the proper folding and maturation of proteins in the endoplasmic reticulum (ER) is both aided and monitored by a number of chaperones and folding enzymes in a complex process referred to as ER quality control (QC). ER-QC is compromised under a variety of conditions, collectively termed ER stress, which cause the accumulation of misfolded proteins in the ER lumen. Eukaryotic cells cope with ER stress by activating a multi-layered protective response, the unfolded protein response (UPR), which adapts the secretory pathway to the ER protein load and increases the efficiency of protein folding. In fungi and animals, O-mannosylation is an essential protein modification that is initiated in the ER by a conserved family of protein O-mannosyltransferases (PMTs). It was recently observed that O-mannosylation of membrane and secretory proteins is especially crucial during ER stress; however, molecular functions and mechanisms are poorly understood.
In this project we want to dissect the role of protein O-mannosylation with respect to ER homeostasis during stress conditions.
People involved: Christina Hölscher, Joan Castells-Ballester, Patrick Neubert, Anke Metschies
Structural and functional characterization of O-mannosyl glycans in mammals
Protein O-mannosylation is conserved from yeast to humans and defines a new pathomechanism of neuromuscular diseases. We established an MS-based workflow and specific tools for the detection of O-mannosyl glycans that resulted in the identification of cadherins as mono-O-mannosylated proteins. We continue to screen for novel substrates of O-mannosylation and to study the impact of these glycans on the performance of the carrier proteins.
People involved: Markus Bartels
Latest News
31. October 2016:
We celebrate our group's attendance of this year's EMBO Conference: Structure and function of the ER in Girona, Spain, which was rewarded with one of two Poster Prizes sponsored by The FEBS Journal. We wish to express our graditute for all the constructive feedback to our research and thank everybody for the interest vested into the field of protein O-mannosylation. We thank the attendants for all the exciting and insightful discussions and the organizers for the arrangement of this wonderful conference series.
Latest Publications
Bartels M.F., Winterhalter P.R., Yu J., Liu Y., Lommel M., Möhrlen F., Hu H., Feizi T., Westerlind U., Ruppert T. and Strahl S. (2016) Protein O-Mannosylation in the Murine Brain: Occurrence of Mono-O-Mannosyl Glycans and Identification of New Substrates. PlosOne [Accepted]
Bausewein D, Engel J, Jank T, Schoedl, M and Strahl, S (2016). Functional similarities between the protein O-mannosyltransferases Pmt4 from baker's yeast and human POMT1. J Biol Chem. 291(34):18006-15. doi: 10.1074/jbc.M116.739128.
Carvalho, S, Oliveira, T, Bartels, MF, Miyoshi, E, Pierce, M, Taniguchi, N, Carneiro, F, Seruca, R, Reis, CA, Strahl, S and Pinho, SS (2016). O–mannosylation and N-glycosylation: two coordinated mechanisms regulating the tumour suppressor functions of E-cadherin in cancer. Oncotarget. doi: 10.18632/ oncotarget.11245. [Epub ahead of print]