Consortin interacts with connexins both in vitro and in vivo. (A) Pulldown experiments of different in vitro synthesized and radioactively labeled connexins (Cx26, Cx30, Cx31, Cx32, Cx43 and Cx45) by a batch-purified GST-consortin (short isoform) chimera. For each pulldown assay, three lanes are shown, corresponding to the relevant in vitro translation reaction (input), a control assay with batch-purified GST (GST), and the assay with the appropriate GST chimera (GST-consortin). Bands corresponding to putative connexin monomers and hexamers are indicated by arrows and arrowheads, respectively. Note that the hexamer band is consistently enriched in the GST-consortin pulldown lane, compared with the input lane. (B) In vitro synthesized, radioactively-labeled Cx26 and Cx30 were pulled down by batch-purified GST-consortin-ΔCter synthesized in Escherichia coli, which indicates that connexin binding does not occur through hydrophobic interactions with the putative transmembrane domain of consortin. (C) Pulldown assay of Cx26 from detergent-free lysates of HeLa-Cx26 cells with GST-consortin (short isoform) and GST-consortin-ΔCter chimeras synthesized in E. coli. A band corresponding to putative Cx26 hexamers, detected with an anti-Cx26 antibody, is observed in the GST-consortin-ΔCter lane. In contrast, no band was detected in the GST-consortin lane, indicating that membrane-inserted Cx26 does not interact with the short isoform of consortin. This may be due to a blockade by the transmembrane segment and C-terminal tail of non-membrane-inserted consortin, which are not part of the minimal connexin-interaction region of consortin. (D) Immunoprecipitation of Cx43 from extracts of HeLa cells transiently transfected with expression plasmid pNTCx43. Extracts were immunoprecipitated with an irrelevant monoclonal antibody (anti-myc), anti-Cx43 monoclonal antibody P2D12, or a mixture of anti-Cx43 monoclonal antibodies IF1 and CT1. Bands corresponding to Cx43 and the short isoform of consortin are detected by immunoblotting in the immunoprecipitates obtained with the anti-Cx43 antibodies, but not in those obtained with the irrelevant antibody, indicating that consortin and Cx43 co-precipitate and may interact in vivo. (E) Escherichia coli-synthesized, batch-purified, GST-consortin and GST-consortin-ΔCter do not pulldown in vitro synthesized pannexin 1 (Panx1).