Long chain polyunsaturated fatty acids are required for efficient neurotransmission in C. elegans

Giovanni M. Lesa, Mark Palfreyman, David H. Hall, M. Thomas Clandinin, Claudia Rudolph, Erik M. Jorgensen, Giampietro Schiavo

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

The complex lipid constituents of the eukaryotic plasma membrane are precisely controlled in a cell-type-specific manner, suggesting an important, but as yet, unknown cellular function. Neuronal membranes are enriched in long-chain polyunsaturated fatty acids (LC-PUFAs) and alterations in LC-PUFA metabolism cause debilitating neuronal pathologies. However, the physiological role of LC-PUFAs in neurons is unknown. We have characterized the neuronal phenotype of C. elegans mutants depleted of LC-PUFAs. The C. elegans genome encodes a single Δ6-desaturase gene (fat-3), an essential enzyme for LC-PUFA biosynthesis. Animals lacking fat-3 function do not synthesize LC-PUFAs and show movement and egg-laying abnormalities associated with neuronal impairment. Expression of functional fat-3 in neurons, or application of exogenous LC-PUFAs to adult animals rescues these defects. Pharmacological, ultrastructural and electrophysiological analyses demonstrate that fat-3 mutant animals are depleted of synaptic vesicles and release abnormally low levels of neurotransmitter at cholinergic and serotonergic neuromuscular junctions. These data indicate that LC-PUFAs are essential for efficient neurotransmission in C. elegans and may account for the clinical conditions associated with mis-regulation of LC-PUFAs in humans.

Original languageEnglish (US)
Pages (from-to)4965-4975
Number of pages11
JournalJournal of cell science
Volume116
Issue number24
DOIs
StatePublished - Dec 15 2003

    Fingerprint

Keywords

  • C. elegans
  • Neuromuscular junction
  • Neurotransmitter release
  • Polyunsaturated fatty acids
  • Synapse

ASJC Scopus subject areas

  • Cell Biology

Cite this

Lesa, G. M., Palfreyman, M., Hall, D. H., Clandinin, M. T., Rudolph, C., Jorgensen, E. M., & Schiavo, G. (2003). Long chain polyunsaturated fatty acids are required for efficient neurotransmission in C. elegans. Journal of cell science, 116(24), 4965-4975. https://doi.org/10.1242/jcs.00918