Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1.
MetadataShow full item record
Connexin 43 (Cx43) is a gap junction (GJ) protein widely expressed in mammalian tissues that mediates cell-to-cell coupling. Intercellular channels comprising GJ aggregates form from docking of paired connexons, with one each contributed by apposing cells. Zonula occludens-1 (ZO-1) binds the carboxy terminus of Cx43, and we have previously shown that inhibition of the Cx43/ZO-1 interaction increases GJ size by 48 h. Here we demonstrated that increases in GJ aggregation occur within 2 h (∼Cx43 half-life) following disruption of Cx43/ZO-1. Immunoprecipitation and Duolink protein-protein interaction assays indicated that inhibition targets ZO-1 binding with Cx43 in GJs as well as connexons in an adjacent domain that we term the "perinexus." Consistent with GJ size increases being matched by decreases in connexons, inhibition of Cx43/ZO-1 reduced the extent of perinexal interaction, increased the proportion of connexons docked in GJs relative to undocked connexons in the plasma membrane, and increased GJ intercellular communication while concomitantly decreasing hemichannel-mediated membrane permeance in contacting, but not noncontacting, cells. ZO-1 small interfering RNA and overexpression experiments verified that loss and gain of ZO-1 function govern the transition of connexons into GJs. It is concluded that ZO-1 regulates the rate of undocked connexon aggregation into GJs, enabling dynamic partitioning of Cx43 channel function between junctional and proximal nonjunctional domains of plasma membrane.
- All Faculty Deposits 
Showing items related by title, author, creator and subject.
Microtubule interactions and regulation of the mitotic kinesin-like protein-1 and kinesin-like calmodulin-binding protein Deavours, Bettina Edith (Virginia Tech, 2001-12-04)Microtubules are essential for many dynamic processes occurring within eukaryotic cells including organelle and vesicular trafficking, motility of cilia and flagella, and mitosis. Microtubules operate in conjunction with ...
GENERATION OF BACULOVIRUS-BRUCELLA ABORTUS HEAT SHOCK PROTEIN RECOMBINANTS; MICE IMMUNE RESPONSES AGAINST THE RECOMBINANTS, AND B. ABORTUS SUPEROXIDE DISMUTASE AND L7/L12 RECOMBINANT PROTEINS Bea, Joo-eun (Virginia Tech, 1999-02-05)Brucella abortus is capable of resisting the microbicidal mechanisms of phagocytic cells and growing within phagocytic cells, usually macrophages. B. abortus, like several other intracellular bacteria responds to the ...
Demonstration of peptide and free amino acid absorption by sheep forestomach epithelium using parabiotic chambers and identification of H+/peptide and free amino acid transport proteins in sheep omasal epithelium and bO2 amino acid transport proteins in pig jejunal epithelium by expression of mRNA in Xenopus laevis oocytes Matthews, James Clyde (Virginia Tech, 1995-04-12)Not available until OCRd