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).
The Ly-6/neurotoxin-like protein1 precursor, Lynx1. The NMR structure is available (Lyukmanova et al. 2011).
Lynx1 of Homo sapiens
Ly6/PLAUR domain-containing protein of 183 aas
Ly6/PLAUR domain-containing protein of Homo sapiens
The secreted Ly-6/uPAR-related protein, SLURP-1 of 103 aas and 1 or 2 TMSs. It is found in epithelium, sensory neurons and immune cells. Point mutations in the slurp-1 gene cause the autosomal inflammation skin disease, Mal de Meleda. SLURP-1 is considered an autocrine/paracrine hormone that regulates growth and differentiation of keratinocytes and controls inflammation and malignant cell transformation. The antiproliferative activity of SLURP-1 is related to the 'metabotropic' signaling pathway through α7-nAChR, that activates intracellular signaling cascades without opening the receptor channel (Lyukmanova et al. 2016). Thus, SLURP-1 is an allosteric antogonist of the α7 nicotinic acetylcholine receptor.
SLURP-1 of Homo sapiens
Prostate and testis expressed protein 4, PATE4 or SVS VII, is a heat labile phospholipid binding protein of 99 aas with 1 N-terminal TMS. It enhances sperm motility and binds to calmodulin to inhibit calcium transport into spermatozoa. It may also modulate the function of nicotinic acetylcholine receptors (Luo et al. 2001).
PATE4 of Mus musculus