Topic: UBE3A

Neurological disorders can be caused by genetic alterations in many genes; UBE3A is one such gene, as a mutation or deletion in the maternal copy of this gene has been shown to cause Angelman Syndrome (AS). AS is a developmental disorder that affects 1 in 15,000 live births, and is characterized by many symptoms, with seizures being highly penetrant and debilitating. Previous research on the pathological characterization of AS model mice showed an increased seizure susceptibility as well as abnormally high levels of perineuronal net (PNN) fluorescence. Our project aims to determine whether the

The UBE3A gene codes for an E3 ubiquitin ligase and is critical to ensure a proper brain function. Indeed, perturbations of UBE3A dosage or function result in pathological phenotypes. Loss of UBE3A causes the Angelman Syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor delay and seizures, while increased UBE3A copy number or activity are strongly associated with Autism. Importantly, the molecular underpinnings of UBE3A-associated pathogenic mechanisms of neurodevelopmental disorders are still poorly understood. In this project, we study the effects of

The Angelman Syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of the maternally expressed UBE3A gene, which encodes an E3 ubiquitin ligase. Although considerable efforts have been put to dissect UBE3A function in the brain, the pathogenic mechanisms remain largely unknown and effective treatments are not available yet. Being an E3 ubiquitin ligase, defective ubiquitination, which may occur in either nuclear or cytosolic compartments, is thought to be a primary mechanism underlying synaptic dysfunction in AS. Increasing evidence indicates a tight functional interplay betwe

Angelman Syndrome (AS) is a neurodevelopmental disorder with complex symptomatology caused by the loss of maternal allele expression of one single gene in the brain, the ubiquitin E3 ligase UBE3A. Even if the underlying genetic basis of AS has previously been extensively described, the molecular mechanisms regulated by UBE3A ubiquitination in the brain remain highly elusive. Here we provide the first proteomic report of UBE3A-mediated ubiquitination events in a mammalian brain. In order to identify Ube3a substrates, we have combined our previously described bioUb mouse with a new mouse strain