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8.A.31 The Ly-6 Neurotoxin-like Protein1 Precursor (Lynx1) Family

Lynx1 is a neuronal membrane protein (118 aas; 2 TMSs) related by fold to snake α-neurotoxins able to modulate nAChRs. Lynx 1 colocalizes with nAChRs on CNS neurons and physically associates with nAChRs. Single-channel recordings show that lynx1 promotes the largest of three current amplitudes elicited by ACh through α4β2 nAChRs and that lynx1 enhances desensitization. Macroscopic recordings quantified the enhancement of desensitization onset by lynx1 and further showed that it slows recovery from desensitization. Direct interaction of lynx1 with nAChRs results in a novel type of functional modulation and suggest that prototoxins may play important roles in vivo by modulating functional properties of their cognate CNS receptors (Ibanez-Tallon et al., 2002).  The 3-d structure has been solved by NMR, and its action on the AChR has been studied (Lyukmanova et al. 2011).

References associated with 8.A.31 family:

Ibanez-Tallon I., J.M. Miwa, H.L. Wang, N.C. Adams, G.W. Crabtree, S.M. Sine SM, N. Heintz. (2002). Novel modulation of neuronal nicotinic acetylcholine receptors by association with the endogenous prototoxin lynx1. Neuron. 33:893-903. 11906696
Luo, C.W., H.J. Lin, and Y.H. Chen. (2001). A novel heat-labile phospholipid-binding protein, SVS VII, in mouse seminal vesicle as a sperm motility enhancer. J. Biol. Chem. 276: 6913-6921. 11118436
Lyukmanova, E.N., M.A. Shulepko, D. Kudryavtsev, M.L. Bychkov, D.S. Kulbatskii, I.E. Kasheverov, M.V. Astapova, A.V. Feofanov, M.S. Thomsen, J.D. Mikkelsen, Z.O. Shenkarev, V.I. Tsetlin, D.A. Dolgikh, and M.P. Kirpichnikov. (2016). Human Secreted Ly-6/uPAR Related Protein-1 (SLURP-1) Is a Selective Allosteric Antagonist of α7 Nicotinic Acetylcholine Receptor. PLoS One 11: e0149733. 26905431
Lyukmanova, E.N., Z.O. Shenkarev, M.A. Shulepko, K.S. Mineev, D. D'Hoedt, I.E. Kasheverov, S.Y. Filkin, A.P. Krivolapova, H. Janickova, V. Dolezal, D.A. Dolgikh, A.S. Arseniev, D. Bertrand, V.I. Tsetlin, and M.P. Kirpichnikov. (2011). NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1. J. Biol. Chem. 286: 10618-10627. 21252236