lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS

Elapid snake venom neurotoxins exert their effects through high-affinity in teractions with specific neurotransmitter receptors. A novel murine gene, l ynx1, is highly expressed in the brain and contains the cysteine-rich motif characteristic of this class of neurotoxins. Primary sequence and gene str ucture analyses reveal an evolutionary relationship between lynx1 and the L y-6/neurotoxin gene family, lynx1 is expressed in large projection neurons in the hippocampus, cortex, and cerebellum. In cerebellar neurons, lynx1 pr otein is localized to a specific subdomain including the soma and proximal dendrites. lynx1 binding to brain sections correlates with the distribution of nAChRs, and application of lynx1 to Xenopus oocytes expressing nAChRs r esults in an increase in acetylcholine-evoked macroscopic currents. These r esults identify lynx1 as a novel protein modulator for nAChRs in vitro, whi ch could have important implications in the regulation of cholinergic funct ion in vivo.