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First published online November 18, 2003
doi: 10.1242/10.1242/jcs.00918
Research Article |
1 Molecular Neuropathobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
2 Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA
3 Center for C. elegans Anatomy, Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA
4 Nutrition and Metabolism Research Group, University of Alberta, Edmonton, Alberta, T6G 2P5, Canada
5 EleGene AG, Am Klopferspitz 19, 82152 Martinsried, Germany
Author for correspondence: (e-mail: giovanni.lesa{at}ucl.ac.uk)
Accepted 2 October 2003
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 
6-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.
Key words: C. elegans, Neuromuscular junction, Neurotransmitter release, Polyunsaturated fatty acids, Synapse
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