Lynx Prototoxins: Roles of Endogenous Mammalian Neurotoxin-Like Proteins in Modulating Nicotinic Acetylcholine Receptor Function to Influence Complex Biological Processes

In this study, β2∗ nAChR-containing receptors and lynx1 were identified using pull down studies from the mouse brain (Nissen et al., 2018), while ws-lynx1, SLURP-1 and SLURP-2 has been successfully mixed with human brain tissue to pull down multiple nAChR subtypes (Lyukmanova et al., 2016a,b; Thomsen et al., 2016). To support the in vivo interaction studies, a lynx1KO phenotype was ameliorated by crossing these mice into mutant mice null for α7 and β2 nAChR genes (Miwa et al., 2006). These in vivo studies provide an important biological context for the interactions observed within in vitro systems. It should be noted that, even within brain tissues, many of these interactions may take place in the cytoplasm, and may therefore be independent of gating functions on the mature receptor pentamers at the cell surface. Receptor number can be reduced via the co-expression of prototoxin (Puddifoot et al., 2015; Wu et al., 2015; George et al., 2017), suggesting an effect on receptor retention or slowing of receptor maturation. Additional studies have indicated that the receptor complexes that escape to the cell surface may form complexes prototoxins (Nichols et al., 2014; Puddifoot et al., 2015; Wu et al., 2015), retaining their modulatory functions. Except in limited cases, however (Wu et al., 2015; George et al., 2017), prototoxins have been demonstrated to retain functional effects even when they have been cleaved from the GPI-anchor using PI-PLC, suggestive...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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