Cx46 hemichannel modulation by nitric oxide: Role of the fourth transmembrane helix cysteine and its possible involvement in cataract formation

Nitric Oxide : Biology and Chemistry
Mauricio A RetamalGuillermo A Altenberg

Abstract

Under normal conditions, connexin (Cx) hemichannels have a low open probability, which can increase under pathological conditions. Since hemichannels are permeable to relatively large molecules, their exacerbated activity has been linked to cell damage. Cx46 is highly expressed in the lens and its mutations have been associated to cataract formation, but it is unknown whether Cx46 has a role in non-genetic cataract formation (i.e. aging and diabetes). Nitric oxide (NO) is a key element in non-genetic cataract formation and Cx46 hemichannels have been shown to be sensitive to NO. The molecular mechanisms of the effects of NO on Cx46 are unknown, but are likely to result from Cx46 S-nitrosation (also known as S-nitrosylation). In this work, we found that lens opacity was correlated with Cx46 S-nitrosation in an animal model of cataract. Consistent with this result, a NO donor increased Cx46 S-nitrosation and hemichannel opening in HLE-B3 cells (cell line derived from human lens epithelial cells). Mutagenesis studies point to the cysteine located in the fourth transmembrane helix (TM4; human C212, rat C218) as the NO sensor. Electrophysiological studies performed in Xenopus oocytes revealed that rat Cx46 hemichannels are sensitive...Continue Reading

Citations

Jul 8, 2020·International Journal of Molecular Sciences·María F Rozas-VillanuevaMauricio A Retamal
Aug 23, 2020·International Journal of Molecular Sciences·Viviana M BerthoudEric C Beyer
Apr 4, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Mauricio A RetamalGuillermo A Altenberg
May 1, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Kai ZhangXiao-Yuan Mao
Aug 8, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Mauricio A RetamalJimmy Stehberg

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