PT  - JOURNAL ARTICLE
AU  - Condon, Kathryn H.
AU  - Ho, Jianghai
AU  - Robinson, Camenzind G.
AU  - Hanus, Cyril
AU  - Ehlers, Michael D.
TI  - The Angelman Syndrome Protein Ube3a/E6AP Is Required for Golgi Acidification and Surface Protein Sialylation
AID  - 10.1523/JNEUROSCI.1930-11.2013
DP  - 2013 Feb 27
TA  - The Journal of Neuroscience
PG  - 3799--3814
VI  - 33
IP  - 9
4099  - http://www.jneurosci.org/content/33/9/3799.short
4100  - http://www.jneurosci.org/content/33/9/3799.full
SO  - J. Neurosci.2013 Feb 27; 33
AB  - 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.