| Abstract |
Nicotinic acetylcholine receptors (nAChR) are present in many excitable tissues and are found both pre and post-synaptically. Through their non-specific cationic permeability, these nAChRs have excitatory roles in neurotransmission, neuromodulation, synaptic plasticity, and neuroprotection. Thus, nAChR mislocalization or functional deficits are associated with many neurological disease states. Therefore identifying the mechanisms that regulate nAChR expression and function will inform our understanding of normal as well as pathological physiological conditions and offer avenues for potential therapeutic advances. Taking advantage of the genetic tractability of the soil nematode Caenorhabditis elegans, a forward genetic screen was performed to isolate regulators of the vertebrate α7 nAChR homologue ACR-16. From this screen a novel regulator of the ACR-16 receptor was identified, the sarco(endo)plasmic reticulum calcium ATPase sca-1. The sca-1 mutant affects ACR-16 receptor level at the NMJ, receptor functionality, and synaptic transmission. Responses to pressure-ejected nicotine in sca-1 mutants are indistinguishable from wild type, which implies the ACR-16 receptors are mislocalized at the NMJ. Changes in cytosolic baseline calcium levels in sca-1 and other mutants indicates a calcium-driven regulation mechanism of the α7-like NAChR ACR-16.
|
