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• W2148657189 abstract "The mechanisms of action of endogenous modulatory ligands of connexin channels are largely unknown. Previous work showed that protonated aminosulfonates (AS), notably taurine, directly and reversibly inhibit homomeric and heteromeric channels that contain Cx26, a widely distributed connexin, but not homomeric Cx32 channels. The present study investigated the molecular mechanisms of connexin channel modulation by taurine, using hemichannels and junctional channels composed of Cx26 (homomeric) and Cx26/Cx32 (heteromeric). The addition of a 28-amino acid tag to the carboxyl-terminal domain (CT) of Cx26 (Cx26(T)) eliminated taurine sensitivity of homomeric and heteromeric hemichannels in cells and liposomes. Cleavage of all but four residues of the tag (Cx26(Tc)) resulted in taurine-induced pore narrowing in homomeric hemichannels, and restored taurine inhibition of heteromeric hemichannels (Cx26(Tc)/Cx32). Taurine actions on junctional channels were fully consistent with those on hemichannels. Taurine-induced inhibition of Cx26/Cx32(T) and nontagged Cx26 junctional channels was blocked by extracellular HEPES, a blocker of the taurine transporter, confirming that the taurine-sensitive site of Cx26 is cytoplasmic. Nuclear magnetic resonance of peptides corresponding to Cx26 cytoplasmic domains showed that taurine binds to the cytoplasmic loop (CL) and not the CT, and that the CT and CL directly interact. ELISA showed that taurine disrupts a pH-dependent interaction between the CT and the CT-proximal half of the CL. These studies reveal that AS disrupt a pH-driven cytoplasmic interdomain interaction in Cx26-containing channels, causing closure, and that the Cx26CT has a modulatory role in Cx26 function." @default.
• W2148657189 created "2016-06-24" @default.
• W2148657189 creator A5013645251 @default.
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• W2148657189 creator A5045474515 @default.
• W2148657189 creator A5069294633 @default.
• W2148657189 creator A5070214965 @default.
• W2148657189 date "2011-08-15" @default.
• W2148657189 modified "2023-09-23" @default.
• W2148657189 title "Mechanism for modulation of gating of connexin26-containing channels by taurine" @default.
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• W2148657189 doi "https://doi.org/10.1085/jgp.201110634" @default.
• W2148657189 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3171079" @default.
• W2148657189 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21844220" @default.
• W2148657189 hasPublicationYear "2011" @default.
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