| Polyunsaturated fatty acids influence synaptojanin localization to regulate synaptic vesicle recycling. | |
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MedLine Citation:
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PMID: 18094048 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The lipid polyunsaturated fatty acids are highly enriched in synaptic membranes, including synaptic vesicles, but their precise function there is unknown. Caenorhabditis elegans fat-3 mutants lack long-chain polyunsaturated fatty acids (LC-PUFAs); they release abnormally low levels of serotonin and acetylcholine and are depleted of synaptic vesicles, but the mechanistic basis of these defects is unclear. Here we demonstrate that synaptic vesicle endocytosis is impaired in the mutants: the synaptic vesicle protein synaptobrevin is not efficiently retrieved after synaptic vesicles fuse with the presynaptic membrane, and the presynaptic terminals contain abnormally large endosomal-like compartments and synaptic vesicles. Moreover, the mutants have abnormally low levels of the phosphoinositide phosphatase synaptojanin at release sites and accumulate the main synaptojanin substrate phosphatidylinositol 4,5-bisphosphate at these sites. Both synaptobrevin and synaptojanin mislocalization can be rescued by providing exogenous arachidonic acid, an LC-PUFA, suggesting that the endocytosis defect is caused by LC-PUFA depletion. By showing that the genes fat-3 and synaptojanin act in the same endocytic pathway at synapses, our findings suggest that LC-PUFAs are required for efficient synaptic vesicle recycling, probably by modulating synaptojanin localization at synapses. |
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Authors:
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Esther Marza; Toni Long; Adolfo Saiardi; Marija Sumakovic; Stefan Eimer; David H Hall; Giovanni M Lesa |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-12-19 |
Journal Detail:
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Title: Molecular biology of the cell Volume: 19 ISSN: 1939-4586 ISO Abbreviation: Mol. Biol. Cell Publication Date: 2008 Mar |
Date Detail:
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Created Date: 2008-02-29 Completed Date: 2008-11-10 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 833-42 Citation Subset: IM |
Affiliation:
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MRC Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, United Kingdom. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acyltransferases
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metabolism Animals Arachidonic Acid / pharmacology Cadherins / metabolism Caenorhabditis elegans / cytology, drug effects, enzymology*, ultrastructure Caenorhabditis elegans Proteins / metabolism Cell Membrane / drug effects, ultrastructure Endocytosis* / drug effects Epidermal Growth Factor / metabolism Fatty Acids, Unsaturated / metabolism* Locomotion / drug effects Mutation / genetics Nerve Tissue Proteins / metabolism* Phosphatidylinositol 4,5-Diphosphate / metabolism Phosphoric Monoester Hydrolases / metabolism* Protein Transport / drug effects R-SNARE Proteins / metabolism Synaptic Vesicles / drug effects, enzymology*, ultrastructure |
| Grant Support | |
ID/Acronym/Agency:
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RR12596/RR/NCRR NIH HHS; //Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Cadherins; 0/Caenorhabditis elegans Proteins; 0/Fatty Acids, Unsaturated; 0/Nerve Tissue Proteins; 0/Phosphatidylinositol 4,5-Diphosphate; 0/R-SNARE Proteins; 0/fat3 protein, C elegans; 506-32-1/Arachidonic Acid; 62229-50-9/Epidermal Growth Factor; EC 2.3.-/Acyltransferases; EC 2.3.1.52/2-acylglycerophosphate acyltransferase; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.-/synaptojanin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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