| Essential role of ELOVL4 in very long chain fatty acid synthesis and retinal function. | |
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MedLine Citation:
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PMID: 22199362 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Very long chain polyunsaturated fatty acid (VLC-PUFA) containing glycerophospholipids are highly enriched in the retina, however details regarding the specific synthesis and function of these highly unusual retinal glycerophospholipids are lacking. ELOVL4 has been identified as a fatty acid elongase protein involved in the synthesis of VLC-PUFAs. Mutations in ELOVL4 have also been implicated in an autosomal dominant form of Stargardt disease (STGD3), a type of juvenile macular degeneration. We have generated photoreceptor specific conditional knockout mice and have used high performance liquid chromatography-mass spectrometry (HPLC-MS) to examine and analyze the fatty acid composition of retinal membrane glycerophosphocholine (PC) and glycerophosphoethanolamine (PE) species. We also used immunofluorescent staining and histology, coupled with electrophysiological data, to assess retinal morphology and visual response. The conditional knockout mice showed a significant decrease in retinal glycerophospholipids containing VLC-PUFAs, specifically contained in the sn-1 position of PCs, implicating the role of Elovl4 in their synthesis. Conditional knockout mice were also found to have abnormal accumulation of lipid droplets and lipofuscin-like granules, while demonstrating photoreceptor-specific abnormalities in visual response, indicating the critical role of Elovl4 for proper rod or cone photoreceptor function. Together, this study demonstrates the essential role of ELOVL4 in VLC-PUFA synthesis and retinal function. |
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Authors:
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Richard Harkewicz; Hongjun Du; Zongzhong Tong; Hisham Alkuraya; Matthew Bedell; Woong Sun; Xiaolei Wang; Yuan-Hao Hsu; Julian Esteve-Rudd; Guy Hughes; Zhiguang Su; Ming Zhang; Vanda S Lopes; Robert S Molday; David S Williams; Edward A Dennis; Kang Zhang |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-24 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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UC San Diego, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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