The ly-6 protein, lynxl, is an endogenous inhibitor of nicotinic signaling in airway epithelium

摘要

In this study, we show that the similarity between neu-rotransmitter signaling in neurons and in BEC extend to the level of transmitter receptor allosteric modulators. The ly-6 family of proteins, also known as three-finger toxins or proteins, is a large family of proteins characterized by precisely spaced cysteine motifs (15, 21, 44). A number of these proteins bind to nAChR and act as positive or negative allosteric modulators. In particular lynxl, originally isolated by Miwa et al. (26) based on its homology with the nicotinic antagonist a-bungarotoxin (aBGT), acts as an endogenous negative regulator of nicotinic signaling in neurons (20, 27). The nAChR are ligand-gated ion channels, and the binding of their endogenous ligand (ACh) or the exogenous ligand nicotine allows entry of Na+ or Ca++ into the cell (25). Binding of lynxl to the nAChR decreases nicotine and ACh-induced currents and increases desensitization. Multiple other members of the ly-6 family also modulate nAChR activity, including Iynx2 (43), slurp-l(3, 6), slurp-2 (2), prostate stem cell antigen (19), and the prostate and testis expressed proteins (24). Because our laboratory has previously shown that lynxl is highly expressed in airway epithelial cells, it would seem likely that lynxl might also regulate nAChR responses to nicotine and ACh in lung (39).