The functional role of protein O-mannosylation

• Applicant: Professorin Dr. Sabine Strahl
• Subject Area: Cell Biology
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 54554815

Protein O-mannosylation represents an evolutionarily conserved, essential post-translational modification with immense impact on a variety of cellular processes. In humans, defects in O-mannosylation lead to Walker-Warburg syndrome, a severe congenital muscular dystrophy associated with defects in neuronal migration. In mouse and yeasts, loss of O-mannosylation causes lethality. In yeasts/fungi, O-mannosylation is indispensable for cell wall integrity, cell morphogenesis and maintenance of cell polarity, however, the molecular basis is only very poorly understood. We want to elucidate the molecular function of O-mannosyl glycans synthesized by different protein Omannosyltransferase complexes and examine the role of O-mannosylation in cell wall integrity, morphogenesis and cell polarity. Using fission yeast as model organism, we will combine classical genetic methods and genomics with molecular, cell biological and biochemical methods to identify and characterize O-mannosylated proteins that are important for viability of yeast. In particular, we will focus on proteins that are vital for cell wall integrity and cell polarity. Further, our analyses will identify components and pathways that compensate the lack of distinct protein Omannosyltransferases. Our studies will significantly improve our understanding of protein O-mannosylation and identify new O-mannosylated proteins which are likely to be crucial for general aspects of fungal growth and development.

• DFG Programme: Research Grants