by Keyword: Connexin-43
Qi, C, Gutierrez, SS, Lavriha, P, Othman, A, Lopez-Pigozzi, D, Bayraktar, E, Schuster, D, Picotti, P, Zamboni, N, Bortolozzi, M, Gervasio, FL, Korkhov, VM, (2023). Structure of the connexin-43 gap junction channel in a putative closed state Elife 12, RP87616 
Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring cells and enabling direct exchange of ions and small molecules. Cell coupling via connexin-43 (Cx43) GJCs is important in a wide range of cellular processes in health and disease (Churko and Laird, 2013; Liang et al., 2020; Poelzing and Rosenbaum, 2004), yet the structural basis of Cx43 function and regulation has not been determined until now. Here, we describe the structure of a human Cx43 GJC solved by cryo-EM and single particle analysis at 2.26 Å resolution. The pore region of Cx43 GJC features several lipid-like densities per Cx43 monomer, located close to a putative lateral access site at the monomer boundary. We found a previously undescribed conformation on the cytosolic side of the pore, formed by the N-terminal domain and the transmembrane helix 2 of Cx43 and stabilized by a small molecule. Structures of the Cx43 GJC and hemichannels (HCs) in nanodiscs reveal a similar gate arrangement. The features of the Cx43 GJC and HC cryo-EM maps and the channel properties revealed by molecular dynamics simulations suggest that the captured states of Cx43 are consistent with a closed state.© 2023, Qi, Acosta Gutierrez et al.
JTD Keywords: cryo-em, dehydroepiandrosterone dhea, expression, gap junction channel, gene, gja1 mutations, hemichannel, membrane protein, phenotype, protein, structure, system, visualization, Biochemistry, Chemical biology, Connexin-43, Cryo-em, Gap junction channel, Hemichannel, Human, Membrane protein, Molecular biophysics, Oculodentodigital dysplasia, Structural biology, Structure
Casanellas, I, Lagunas, A, Vida, Y, Perez-Inestrosa, E, Rodriguez-Pereira, C, Magalhaes, J, Andrades, JA, Becerra, J, Samitier, J, (2022). Nanoscale ligand density modulates gap junction intercellular communication of cell condensates during chondrogenesis Nanomedicine 17, 775-791
Aim: To unveil the influence of cell-matrix adhesions in the establishment of gap junction intercellular communication (GJIC) during cell condensation in chondrogenesis. Materials & methods: Previously developed nanopatterns of the cell adhesive ligand arginine-glycine-aspartic acid were used as cell culture substrates to control cell adhesion at the nanoscale. In vitro chondrogenesis of mesenchymal stem cells was conducted on the nanopatterns. Cohesion and GJIC were evaluated in cell condensates. Results: Mechanical stability and GJIC are enhanced by a nanopattern configuration in which 90% of the surface area presents adhesion sites separated less than 70 nm, thus providing an onset for cell signaling. Conclusion: Cell-matrix adhesions regulate GJIC of mesenchymal cell condensates during in vitro chondrogenesis from a threshold configuration at the nanoscale.
JTD Keywords: arginine-glycine-aspartic acid, arginine–glycine–aspartic acid, cell adhesion, condensation, dendrimer-based nanopatterning, gap junction intercellular communication, Actin, Adhesion, Arginine-glycine-aspartic acid, Cell adhesion, Collagen, Condensation, Connexin-43, Dendrimer-based nanopatterning, Dynamics, Extracellular-matrix, Fibronectin, Gap junction intercellular communication, Mesenchymal stem cells, Permeability, Phenotype, Vinculin
