Human Three-Finger Protein Lypd6 Is a Negative Modulator of the Cholinergic System in the Brain.

ABSTRACT: Lypd6 is a GPI-tethered protein from the Ly-6/uPAR family expressed in the brain. Lypd6 enhances the Wnt/β-catenin signaling, although its action on nicotinic acetylcholine receptors (nAChRs) have been also proposed. To investigate a cholinergic activity of Lypd6, we studied a recombinant water-soluble variant of the human protein (ws-Lypd6) containing isolated "three-finger" LU-domain. Experiments at different nAChR subtypes expressed in Xenopus oocytes revealed the negative allosteric modulatory activity of ws-Lypd6. Ws-Lypd6 inhibited ACh-evoked currents at α3β4- and α7-nAChRs with IC₅₀ of ∼35 and 10 μM, respectively, and the maximal amplitude of inhibition of 30-50%. EC₅₀ of ACh at α3β4-nAChRs (∼30 μM) was not changed in the presence of 35 μM ws-Lypd6, whil

SUBMITTER: Kulbatskii D 

PROVIDER: S-EPMC8494132 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature