title: Regulation of gap junction channels and hemichannels by phosphorylation and redox changes: a revision.
abstract: Post-translational modifications of connexins play an important role in the regulation of gap junction and hemichannel permeability. The prerequisite for the formation of functional gap junction channels is the assembly of connexin proteins into hemichannels and their insertion into the membrane. Hemichannels can affect cellular processes by enabling the passage of signaling molecules between the intracellular and extracellular space. For the intercellular communication hemichannels from one cell have to dock to its counterparts on the opposing membrane of an adjacent cell to allow the transmission of signals via gap junctions from one cell to the other. The controlled opening of hemichannels and gating properties of complete gap junctions can be regulated via post-translational modifications of connexins. Not only channel gating, but also connexin trafficking and assembly into hemichannels can be affected by post-translational changes. Recent investigations have shown that connexins can be modified by phosphorylation/dephosphorylation, redox-related changes including effects of nitric oxide (NO), hydrogen sulfide (H2S) or carbon monoxide (CO), acetylation, methylation or ubiquitination. Most of the connexin isoforms are known to be phosphorylated, e.g. Cx43, one of the most studied connexin at all, has 21 reported phosphorylation sites. In this review, we provide an overview about the current knowledge and relevant research of responsible kinases, connexin phosphorylation sites and reported effects on gap junction and hemichannel regulation. Regarding the effects of oxidants we discuss the role of NO in different cell types and tissues and recent studies about modifications of connexins by CO and H2S.
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München and Munich University Hospital, München, Germany. kristin.pogoda@lrz.uni-muenchen.de.|DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, München, Germany. kristin.pogoda@lrz.uni-muenchen.de.
authors.forename: Kristin
authors.initials: K
authors.lastname: Pogoda
authors.affiliation: Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-Universität München and Munich University Hospital, München, Germany.|DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, München, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kameritsch
authors.affiliation: Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Retamal
authors.affiliation: Experimental Physiology Laboratory (EPhyL), Antofagasta Institute, Universidad de Antofagasta, Antofagasta, Chile.
authors.forename: José L
authors.initials: JL
authors.lastname: Vega
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism
chemical_list: D007473:Ion Channels; D002248:Carbon Monoxide; D011494:Protein Kinases; D006862:Hydrogen Sulfide
keywords: Channels; Gap junction; Hemichannel; Nitric Oxide; Phosphorylation; Redox