TY - JOUR T1 - The Angelman Syndrome Protein Ube3a/E6AP Is Required for Golgi Acidification and Surface Protein Sialylation JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3799 LP - 3814 DO - 10.1523/JNEUROSCI.1930-11.2013 VL - 33 IS - 9 AU - Kathryn H. Condon AU - Jianghai Ho AU - Camenzind G. Robinson AU - Cyril Hanus AU - Michael D. Ehlers Y1 - 2013/02/27 UR - http://www.jneurosci.org/content/33/9/3799.abstract N2 - Angelman syndrome (AS) is a severe disorder of postnatal brain development caused by neuron-specific loss of the HECT (homologous to E6AP carboxy terminus) domain E3 ubiquitin ligase Ube3a/E6AP. The cellular role of Ube3a remains enigmatic despite recent descriptions of synaptic and behavioral deficits in AS mouse models. Although neuron-specific imprinting is thought to limit the disease to the brain, Ube3a is expressed ubiquitously, suggesting a broader role in cellular function. In the current study, we demonstrate a profound structural disruption and cisternal swelling of the Golgi apparatus (GA) in the cortex of AS (UBE3Am−/p+) mice. In Ube3a knockdown cell lines and UBE3Am−/p+ cortical neurons, the GA is severely under-acidified, leading to osmotic swelling. Both in vitro and in vivo, the loss of Ube3a and corresponding elevated pH of the GA is associated with a marked reduction in protein sialylation, a process highly dependent on intralumenal Golgi pH. Altered ion homeostasis of the GA may provide a common cellular pathophysiology underlying the diverse plasticity and neurodevelopmental deficits associated with AS. ER -