title: Na+/K+ ATPase regulates the expression and localization of acetylcholine receptors in a pump activity-independent manner.
abstract: Na+/K+ ATPase is a plasma membrane-localized sodium pump that maintains the ion gradients between the extracellular and intracellular environments, which in turn controls the cellular resting membrane potential.Recent evidence suggests that the pump is also localized at synapses and regulates synaptic efficacy.However, its precise function at the synapse is unknown. Here we show that two mutations in the alpha subunit of the eat-6 Na+/K+ ATPase in Caenorhabditis elegans dramatically increase the sensitivity to acetylcholine(Ach) agonists and alter the localization of nicotinic Ach receptors at the neuromuscular junction (NMJ).These defects can be rescued by mutated EAT-6 proteins which lack its pump activity, suggesting the presence of a novel function for Ach signaling. The Na+/K+ ATPase accumulates at postsynaptic sites and appears to surround Ach receptors to maintain rigid clusters at the NMJ. Our findings suggest a pump activity-independent, allele-specific role for Na+/K+ ATPase on postsynaptic organization and synaptic efficacy.
authors.affiliation: Neuroscience Research Institute, AIST, Tsukuba, Ibaraki 305-8566, Japan. doi-m@aist.go.jp
authors.forename: Motomichi
authors.initials: M
authors.lastname: Doi
authors.forename: Kouichi
authors.initials: K
authors.lastname: Iwasaki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D011950:Receptors, Cholinergic / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D011950:Receptors, Cholinergic; D000254:Sodium-Potassium-Exchanging ATPase