The functional role of protein O-mannosyltransferase POMT2 for mammalian development and fertilization

• Applicant: Professorin Dr. Sabine Strahl
• Subject Area: Cell Biology
• Term: from 2004 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5439716

Protein O-mannosylation is a crucial protein modification in uni- and multicellular eukaryotes. In humans defects in O-mannosyl glycan synthesis result in neuromuscular diseases. Protein O-mannosylation is initiated by an evolutionarily conserved family of protein Omannosyltransferases (PMTs). In mammals two PMT family members are present namely POMT1 and POMT2 which act in a complex. Mutations in the human POMT1 gene cause Walker-Warburg syndrome, a severe congenital neuromuscular dystrophy. Several lines of evidence suggest that also POMT2 is a candidate gene of Walker-Warburg syndrome. We cloned mouse Pomt2 and showed that in addition to the somatic enzyme a sperm specific isoform exists that localizes to the acrosome a sperm specific organell that is essential for fertilization. The major objective of this project is to elucidate the functional role of mammalian POMT2 in somatic and reproductive cells by investigating enzyme activities, (sub)cellular expression and localization in adult tissues and during embryonic development using mouse as a model system. In addition, generating targeted deletion of POMT2 in mouse will allow us to study POMT2 function in vivo and to establish an animal model for neuromuscular diseases that are caused by lack of O-mannosyl glycans.

• DFG Programme: Research Grants