Long chain polyunsaturated fatty acids are required for efficient neurotransmission in C. elegans.
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 Delta6-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.
Lesa
Giovanni M
GM
Molecular Neuropathobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Palfreyman
Mark
M
Hall
David H
DH
Clandinin
M Thomas
MT
Rudolph
Claudia
C
Jorgensen
Erik M
EM
Schiavo
Giampietro
G
D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004594:Electrophysiology; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D001523:Mental Disorders / Q000378:metabolism; D008969:Molecular Sequence Data; D009424:Nervous System Physiological Phenomena; D009469:Neuromuscular Junction / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000378:metabolism*
D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D005231:Fatty Acids, Unsaturated; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D044263:Receptors, Serotonin, 5-HT1; C477784:fat-3 protein, C elegans; D004815:Epidermal Growth Factor