A Drosophila model for studying neurological defects associated with Congenital Disorder of Glycosylation type IIe

The term glycosylation describes the enzymatic addition of oligosaccharide moieties to proteins or lipids. This process has been implicated in several cellular reactions including protein folding, self-non-self recognition, cell signaling and cell adhesion. More than 70 monogenic congenital disorders of glycosylation (CDG) have been described that are caused by defective synthesis of glycoconjugates. Most of these diseases are associated with neurological manifestations. Patients suffering from COG7-CDG typically present with microcephaly, epileptic seizures, and brain atrophy. Published studies have revealed the under-glycosylation of proteins in COG7-CDG and other CDG patients. However the correlation between impaired synthesis of glycoproteins and the pathological loss of neurological functions remains unknown and the there are no effective therapeutics for these patients. We will use Drosophila melanogaster as a model system to investigate the molecular mechanisms causing the COG7-neurological features. Fruit flies offer unique opportunities for genetic manipulation. Moreover given the complexity and the redundancy of glycosylation enzymes in vertebrate cells, Drosophila represents an attractive model system to investigate neural-specific glycosylation defects at a simplified level.