Arachidonic Acid is Essential for Normal Touch Sensation

Abstract

Touch, proprioception, and blood pressure regulation rely on mechanoreceptor neurons and mechano-electrical transduction (MeT) channels to convert mechanical cues into electrical signals. The protein partners that form native MeT channels are known only for a small group of mechanoreceptor neurons, including the touch receptor neurons responsible for gentle body touch in C. elegans. Such MeT channels are formed from at least four membrane proteins: two amiloride-sensitive sodium channel proteins (MEC-4 and MEC-10) and two putative lipid binding protein subunits (MEC-2 and MEC-6). It remains unknown how touch activates MeT channels, but interactions between the channel and the lipid membrane are likely to be essential. To learn more about interactions between MeT channels and specific lipids, we utilized C. elegans strains deficient in the synthesis of long-chain, poly-unsaturated fatty acids (PUFAs) and identified arachidonic acid (AA) as the sole PUFA required for full touch sensitivity. Touch receptor neurons retain normal morphology in PUFA-deficient mutants and normal touch sensitivity can be restored by exogenous PUFAs. We will present evidence garnered from behavioral and optogenetic studies suggesting that long-chain PUFAs are needed to activate native MeT channels, but dispensable for subsequent events linking sensory signaling in touch receptor neurons to behavior. Our data suggest that AA and its non-metabolizable analog ETYA directly modulate the activity of the MeT channel.