Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans.
作者： Alexander Gottschalk , Ruta B Almedom , Thorsten Schedletzky , Scott D Anderson , John R Yates
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摘要: Nicotinic acetylcholine receptors (nAChRs) mediate fast excitatory neurotransmission in neurons and muscles. To identify nAChR accessory proteins, which may regulate their expression or function, we performed tandem affinity purification of the levamisole-sensitive from Caenorhabditis elegans, mass spectrometry associated components, RNAi-based screening for effects on vivo nicotine sensitivity. Among proteins identified was calcineurin A subunit TAX-6, appeared to function as a negative regulator activity. We also five not previously linked whose inactivation conferred resistance, implicating them positive regulators Of these, copine NRA-1 colocalized with levamisole receptor at neuronal muscle plasma membranes, and, when mutated, caused reduced synaptic expression. Loss SOC-1, acts tyrosine kinase (RTK) signaling, levels, did mutations fibroblast growth factor EGL-15, another RTK, CAM-1. Thus, is viable approach novel regulating neurotransmitter activity model systems like C. elegans.
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