Activity-dependent changes in MAPK activation in the Angelman Syndrome mouse model

Learning & Memory
Irina FilonovaEdwin J Weeber


Angelman Syndrome (AS) is a devastating neurological disorder caused by disruption of the maternal UBE3A gene. Ube3a protein is identified as an E3 ubiquitin ligase that shows neuron-specific imprinting. Despite extensive research evaluating the localization and basal expression profiles of Ube3a in mouse models, the molecular mechanisms whereby Ube3a deficiency results in AS are enigmatic. Using in vitro and in vivo systems we show dramatic changes in the expression of Ube3a following synaptic activation. In primary neuronal culture, neuronal depolarization was found to increase both nuclear and cytoplasmic Ube3a levels. Analogous up-regulation in maternal and paternal Ube3a expression was observed in Ube3a-YFP reporter mice following fear conditioning. Absence of Ube3a led to deficits in the activity-dependent increases in ERK1/2 phosphorylation, which may contribute to reported deficits in synaptic plasticity and cognitive function in AS mice. Taken together, our findings provide novel insight into the regulation of Ube3a by synaptic activity and its potential role in kinase regulation.


Oct 7, 2015·Frontiers in Neuroscience·Gabrielle L Sell, Seth S Margolis
Apr 14, 2015·The European Journal of Neuroscience·Whitney R HethornEdwin J Weeber
Apr 14, 2015·Nature Neuroscience·Jeremy ValluyGerhard Schratt
Mar 31, 2015·PloS One·Elisa Aguilar-MartinezAndrew D Sharrocks
Dec 24, 2019·Journal of Neuroscience Research·Xin Yang

Related Concepts

Establishment and Maintenance of Localization
MAPK3 wt Allele
Resting Potentials
Protein Phosphorylation
Synaptic Transmission
UBE3A Gene (Procedure)
Activation of Mapk Activity

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Angelman Syndrome

Angelman syndrome is a neurogenetic imprinting disorder caused by loss of the maternally inherited UBE3A gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Here is the latest research.