Document Detail


Polyunsaturated fatty acids influence synaptojanin localization to regulate synaptic vesicle recycling.
MedLine Citation:
PMID:  18094048     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Esther Marza; Toni Long; Adolfo Saiardi; Marija Sumakovic; Stefan Eimer; David H Hall; Giovanni M Lesa
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-12-19
Journal Detail:
Title:  Molecular biology of the cell     Volume:  19     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-29     Completed Date:  2008-11-10     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  833-42     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acyltransferases / 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:
MC_U122663296//Medical Research Council; MC_U122680443//Medical Research Council; RR12596/RR/NCRR NIH HHS; //Medical Research Council
Chemical
Reg. No./Substance:
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; 27YG812J1I/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

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