Human Molecular Genetics Advance Access originally published online on November 7, 2008
Human Molecular Genetics 2009 18(3):454-462; doi:10.1093/hmg/ddn373
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The Drosophila homologue of the Angelman syndrome ubiquitin ligase regulates the formation of terminal dendritic branches
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,¶Gladstone Institute of Neurological Disease and Department of Neurology, University of California, San Francisco, CA 94158, USA
* To whom correspondence should be addressed at: Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA 94158, USA. Tel: +1 4157342514; Fax: +1 4153550824; Email: fgao{at}gladstone.ucsf.edu
Received September 25, 2008; Accepted November 4, 2008
Angelman syndrome is a severe neurodevelopmental disorder mostly caused by loss-of-function mutations in the maternal allele of UBE3A, a gene that encodes an E3 ubiquitin ligase. Drosophila UBE3A (dUBE3A) is highly homologous to human UBE3A (hUBE3A) at the amino acid sequence level, suggesting their functional conservation. We generated dUBE3A-null mutant fly lines and found that dUBE3A is not essential for viability. However, loss of dUBE3A activity reduced dendritic branching of sensory neurons in the peripheral nervous system and slowed the growth of terminal dendritic fine processes. Several lines of evidence indicated that dUBE3A regulates dendritic morphogenesis in a cell autonomous manner. Moreover, overexpression of dUBE3A also decreased dendritic branching, suggesting that the proper level of dUBE3A is critically important for the normal dendritic patterning. These findings suggest that dendritic pathology may contribute to neurological deficits in patients with Angelman syndrome.
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.
Present address: Advanced Cell Diagnostics, Fremont, CA 94555, USA.
¶ Present address: Department of Neurology, Northwestern University, Chicago, IL 60611, USA.