SP21
Principal Investigator: Christian Hübner & Patricia Franzka (Institute of Human Genetics, Jena University Hospital) & Sonnhild Mittag (Institute for Biochemistry II, Jena University Hospital)
Mona Schurig (PhD): Impact of alterations in glycosylation patterns in disease and aging
Glycosylation is the most common posttranslational modification of proteins and lipids. It plays a prominent role in protein stability and conformation, cell-to-cell-communication, cell-matrix-interaction, adhesion, protein targeting and folding. We recently identified mutations in GDP-mannose-pyrophosphorylase-A (GMPPA) in patients suffering from muscle weakness, gait abnormalities, achalasia, alacrima and mental retardation (AAMR syndrome). We could subsequently show that GMPPA acts as an allosteric feedback inhibitor of GMPPB, which catalyzes the production of GDP-mannose, a key substrate for glycosylation. As a consequence, GMPPA defects result in the hyperglycosylation of several proteins. Here, we will use our GMPPA knockout mouse model and different in vitro approaches to assess the consequences of GMPPA defects for brain development and ageing.