Polyunsaturated fatty acids influence synaptojanin localization to regulate synaptic vesicle recycling

Esther Marza, Toni Long, Adolfo Saiardi, Marija Sumakovic, Stefan Eimer, David H. Hall, Giovanni M. Lesa

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)833-842
Number of pages10
JournalMolecular Biology of the Cell
Volume19
Issue number3
DOIs
StatePublished - Mar 2008

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Synaptic Vesicles
Unsaturated Fatty Acids
R-SNARE Proteins
Endocytosis
Synapses
Fats
Synaptic Membranes
Caenorhabditis elegans
Presynaptic Terminals
Phosphatidylinositols
synaptojanin
Arachidonic Acid
Acetylcholine
Serotonin
Lipids
Membranes
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Polyunsaturated fatty acids influence synaptojanin localization to regulate synaptic vesicle recycling. / Marza, Esther; Long, Toni; Saiardi, Adolfo; Sumakovic, Marija; Eimer, Stefan; Hall, David H.; Lesa, Giovanni M.

In: Molecular Biology of the Cell, Vol. 19, No. 3, 03.2008, p. 833-842.

Research output: Contribution to journalArticle

Marza, Esther ; Long, Toni ; Saiardi, Adolfo ; Sumakovic, Marija ; Eimer, Stefan ; Hall, David H. ; Lesa, Giovanni M. / Polyunsaturated fatty acids influence synaptojanin localization to regulate synaptic vesicle recycling. In: Molecular Biology of the Cell. 2008 ; Vol. 19, No. 3. pp. 833-842.
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