Topic: E3 ubiquitin ligase

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 KCNH2 gene-encoded KV11.1 voltage-gated potassium channel, also known as hERG, is abundantly expressed in the heart and brain, and plays an essential role in stabilizing cardiac and neuronal membrane potentials. Loss-of-function KCNH2 mutations, as well as pharmacological suppressions of human KV11.1 channel function, have been associated with arrhythmia and epilepsy. The majority of disease-related mutations involve aberrant KV11.1 protein folding, resulting in enhanced endoplasmic reticulum (ER)-associated degradation and decreased cell-surface protein level. Despite previous identificat

The voltage-dependent chloride channel ClC-2 is a member of the CLC channel/transporter superfamily. A functional ClC-2 channel comprises a dimeric structure, with each monomer containing 18 intracellular or transmembrane α-helices (helices A to R). ClC-2 is ubiquitously expressed and has been detected in astrocytes and oligodendrocytes, where ClC-2 colocalizes with the adhesion molecule GlialCAM at astrocyte-astrocyte junctions. Mutations in human genes encoding ClC-2 or GlialCAM have been linked to the white matter disease leukodystrophy. A disease-causing mutation significantly increasing t

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