BBB seminar: Daan van Aalten
X-linked intellectual disability mutations in O-GlcNAc transferase
Daan van Aalten
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Scotland, UK, and Institute for Precision Medicine, Xiangya Hospital, Central South University, Changsha, China
Protein O-GlcNAcylation is an essential posttranslational modification regulated by two opposing enzymes, O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT). In several animal models, it has been shown that OGT is essential for embryogenesis and early development. A range of proteomics studies have suggested that over a thousand intracellular proteins are O-GlcNAc modified. However, there is only an emerging literature on the biological mechanisms behind the O-GlcNAc sites on these proteins. Intellectual Disability (ID), the most common severe handicap of childhood, is characterized by substantial limitations in cognitive function and adaptive behaviour. At the cellular level, this is reflected by deficits in synaptic structure and plasticity. Very recently, OGT mutations causing ID have been identified in several families, leading to severe intellectual disability, developmental delay, behavioural problems, clinodactyly and microcephaly. I will describe the effects of these mutations in embryonic stem cells and Drosophila melanogaster and our efforts towards uncovering the molecular, biochemical and cellular mechanisms underpinning the neurodevelopmental phenotypes observed in these patients.
Chairperson: Inari Kursula, Department of Biomedicine