Document Detail


The Drosophila homologue of the Angelman syndrome ubiquitin ligase regulates the formation of terminal dendritic branches.
MedLine Citation:
PMID:  18996915     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yubing Lu; Fay Wang; Yan Li; Jacob Ferris; Jin-A Lee; Fen-Biao Gao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-11-07
Journal Detail:
Title:  Human molecular genetics     Volume:  18     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-15     Completed Date:  2009-02-27     Revised Date:  2010-09-22    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  454-62     Citation Subset:  IM    
Affiliation:
Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
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MeSH Terms
Descriptor/Qualifier:
Angelman Syndrome / enzymology,  genetics
Animals
Dendrites / enzymology*,  genetics
Drosophila / enzymology*,  genetics,  growth & development
Drosophila Proteins / genetics,  metabolism*
Humans
Morphogenesis
Peripheral Nervous System / cytology,  enzymology,  growth & development
Sensory Receptor Cells / cytology,  enzymology
Ubiquitin-Protein Ligases / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
HD044752/HD/NICHD NIH HHS; MH079198/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Drosophila Proteins; EC 6.3.2.19/Ube3a protein, Drosophila; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections

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