Linked Life Data

19617635

Source:http://linkedlifedata.com/resource/pubmed/id/19617635

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2009-9-23
pubmed:abstractText
Long-chain acyl-CoA synthetases (ACSLs) convert long-chain fatty acids to acyl-CoAs, the activated substrates essential in various metabolic and signaling pathways. Mutations in ACSL4 are associated with non-syndromic X-linked mental retardation (MRX). However, the developmental functions of ACSL4 and how it is involved in the pathogenesis of MRX remain largely unknown. The Drosophila ACSL-like protein is highly homologous to human ACSL3 and ACSL4, and we designate it as dAcsl. In this study, we demonstrate that dAcsl and ACSL4 are highly conserved in terms of ACSL4's ability to substitute the functions of dAcsl in organismal viability, lipid storage and the neural wiring in visual center. In neurodevelopment, decapentaplegic (Dpp, a BMP-like molecule) production diminished specifically in the larval brain of dAcsl mutants. Consistent with the Dpp reduction, the number of glial cells and neurons dramatically decreased and the retinal axons mis-targeted in the visual cortex. All these defects in Drosophila brain were rescued by the wild-type ACSL4 but not by the mutant products found in MRX patients. Interestingly, expression of an MRX-associated ACSL4 mutant form in a wild-type background led to the lesions in visual center, suggesting a dominant negative effect. These findings validate Drosophila as a model system to reveal the connection between ACSL4 and BMP pathway in neurodevelopment, and to infer the pathogenesis of ACSL4-related MRX.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3894-905
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Analyses of mental dysfunction-related ACSl4 in Drosophila reveal its requirement for Dpp/BMP production and visual wiring in the brain.
pubmed:affiliation
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't