The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo
| Autor: | Sarah L. King, Inés Ibañez-Tallon, Reiko Maki Fitzsimonds, Constantine Pavlides, Barbara J. Caldarone, Nathaniel Heintz, Marina R. Picciotto, Cheng Xiao, Henry A. Lester, Julie M. Miwa, Tanya R. Stevens |
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| Rok vydání: | 2006 |
| Předmět: |
Agonist
Nicotine Allosteric modulator Patch-Clamp Techniques medicine.drug_class Cell Survival Neuroscience(all) Biology Receptors Nicotinic MOLNEURO Membrane Potentials 03 medical and health sciences Mice 0302 clinical medicine medicine LYNX1 Excitatory Amino Acid Agonists Animals Nicotinic Agonists Receptor 030304 developmental biology Acetylcholine receptor Adaptor Proteins Signal Transducing Neurons 0303 health sciences Membrane Glycoproteins General Neuroscience Neurodegeneration Neuropeptides Age Factors Association Learning Brain medicine.disease Mice Mutant Strains Nicotinic agonist nervous system Mutation Nerve Degeneration SYSNEURO Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuron. 51(5):587-600 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2006.07.025 |
| Popis: | Nicotinic acetylcholine receptors (nAChRs) affect a wide array of biological processes, including learning and memory, attention, and addiction. lynx1, the founding member of a family of mammalian prototoxins, modulates nAChR function in vitro by altering agonist sensitivity and desensitization kinetics. Here we demonstrate, through the generation of lynx1 null mutant mice, that lynx1 modulates nAChR signaling in vivo. Its loss decreases the EC(50) for nicotine by approximately 10-fold, decreases receptor desensitization, elevates intracellular calcium levels in response to nicotine, and enhances synaptic efficacy. lynx1 null mutant mice exhibit enhanced performance in specific tests of learning and memory. Consistent with reports that mutations resulting in hyperactivation of nAChRs can lead to neurodegeneration, aging lynx1 null mutant mice exhibit a vacuolating degeneration that is exacerbated by nicotine and ameliorated by null mutations in nAChRs. We conclude that lynx1 functions as an allosteric modulator of nAChR function in vivo, balancing neuronal activity and survival in the CNS. |
| Databáze: | OpenAIRE |
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