loading page

Quantitative automated assays in living cells to screen for inhibitors of hemichannel function
  • +6
  • Emmanuelle Soleilhac,
  • Marjorie Comte,
  • Anaelle da Costa,
  • Caroline Barette,
  • Christèle Picoli,
  • Magda Mortier,
  • Laurence Aubry,
  • Franck Mouthon,
  • Marie-Odile Fauvarque
Emmanuelle Soleilhac

Corresponding Author:[email protected]

Author Profile
Marjorie Comte
University Grenoble Alpes, CEA, Inserm, IRIG, BGE
Author Profile
Anaelle da Costa
Theranexus
Author Profile
Caroline Barette
University Grenoble Alpes, CEA, Inserm, IRIG, BGE
Author Profile
Christèle Picoli
Theranexus
Author Profile
Magda Mortier
University Grenoble Alpes, CEA, Inserm, IRIG, BGE
Author Profile
Laurence Aubry
University Grenoble Alpes, CEA, Inserm, IRIG, BGE
Author Profile
Franck Mouthon
Theranexus
Author Profile
Marie-Odile Fauvarque
University Grenoble Alpes, CEA, Inserm, IRIG, BGE
Author Profile

Abstract

In vertebrates, intercellular communication is largely mediated by connexins, a family of structurally related transmembrane proteins that assemble to form hemichannels (HCs) at the plasma membrane. HCs are upregulated in different brain disorders; hence represent innovative therapeutic targets and identifying modulators of Cx-based HCs is of great interest for better understanding their function and defining new treatments. In this study, we developed automated versions of two different cell-based assays to identify new pharmacological modulators of HCs. The first assay follows the incorporation of a fluorescent dye, Yo-Pro, by real-time imaging while the second is based on the quenching of a fluorescent protein, YFPQL, by iodide after iodide uptake. These assays were then used to screen a collection of 2,242 approved drugs and compounds under development. This study led to the identification of 11 new HC blockers, active in the two assays, with 5 drugs active on HC but not on gap junction (GJ) activities. To our knowledge, this is the first screening on HC activity and our results suggest the potential of a new use of already approved drugs in CNS disorders with HC impairments.
23 Apr 2020Submitted to Biotechnology Journal
23 Apr 2020Assigned to Editor
23 Apr 2020Submission Checks Completed