Publication Date:
2003-03-15
Description:
Mutations in proteins of the Drosophila phototransduction cascade, a prototypic guanine nucleotide-binding protein-coupled receptor signaling system, lead to retinal degeneration and have been used as models to understand human degenerative disorders. Here, modulating the sphingolipid biosynthetic pathway rescued retinal degeneration in Drosophila mutants. Targeted expression of Drosophila neutral ceramidase rescued retinal degeneration in arrestin and phospholipase C mutants. Decreasing flux through the de novo sphingolipid biosynthetic pathway also suppressed degeneration in these mutants. Both genetic backgrounds modulated the endocytic machinery because they suppressed defects in a dynamin mutant. Suppression of degeneration in arrestin mutant flies expressing ceramidase correlated with a decrease in ceramide levels. Thus, enzymes of sphingolipid metabolism may be suitable targets in the therapeutic management of retinal degeneration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Acharya, Usha -- Patel, Shetal -- Koundakjian, Edmund -- Nagashima, Kunio -- Han, Xianlin -- Acharya, Jairaj K -- New York, N.Y. -- Science. 2003 Mar 14;299(5613):1740-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regulation of Cell Growth Laboratory, National Cancer Institute-Frederick, Frederick, MD 21702, USA. acharyau@mail.ncifcrf.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12637747" target="_blank"〉PubMed〈/a〉
Keywords:
Acyltransferases/genetics/metabolism
;
Amidohydrolases/genetics/*metabolism
;
Animals
;
Animals, Genetically Modified
;
Apoptosis
;
Arrestins/genetics/metabolism
;
Ceramidases
;
Ceramides/biosynthesis/*metabolism
;
Clathrin/physiology
;
Cloning, Molecular
;
Crosses, Genetic
;
Drosophila/genetics/*physiology
;
Dynamins/genetics/physiology
;
Electroretinography
;
*Endocytosis
;
Genes, Insect
;
Light
;
Mutation
;
Necrosis
;
Neutral Ceramidase
;
Phosphatidylinositol Diacylglycerol-Lyase
;
Phosphoproteins/genetics/metabolism
;
Photoreceptor Cells, Invertebrate/cytology/*physiology/ultrastructure
;
Receptors, Cell Surface/metabolism
;
Retinal Degeneration/genetics
;
Rhodopsin/metabolism
;
Serine C-Palmitoyltransferase
;
Spectrometry, Mass, Electrospray Ionization
;
Sphingosine/metabolism
;
Type C Phospholipases/genetics/metabolism
;
*Vision, Ocular
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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