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Updated: Feb 6, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
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Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications

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An elusive adenylate cyclase complicit in cholera is exposed

Christoph O Randak1

  • 1Stead Family Department of Pediatrics and the Lung Biology and Cystic Fibrosis Research Center of the Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa 52242.

The Journal of Biological Chemistry
|August 19, 2018
PubMed

Insights

Researchers identified adenylate cyclase isoform 6 (AC6) as the enzyme activating the cystic fibrosis transmembrane conductance regulator (CFTR) channel in cholera. This discovery offers new therapeutic targets for cholera treatment.

Area of Science:

  • Molecular Biology
  • Gastroenterology
  • Ion Channel Physiology

Background:

  • Cholera enterotoxin triggers intestinal fluid secretion by activating the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel.
  • The specific adenylate cyclase enzyme responsible for this pathological CFTR activation has remained unidentified.

Purpose of the Study:

  • To identify the adenylate cyclase enzyme that interacts with and activates the CFTR channel in the intestinal epithelium.
  • To elucidate the molecular mechanisms underlying cholera-induced CFTR hyperactivity.

Main Methods:

  • Investigated the functional and structural association between adenylate cyclase isoforms and CFTR in mouse and human intestinal epithelial cells.
  • Utilized molecular biology techniques to confirm the interaction and functional consequence of AC6 on CFTR activity.

Main Results:

  • Adenylate cyclase isoform 6 (AC6) was identified as the enzyme that functionally and structurally pairs with CFTR in both mouse and human intestinal epithelium.
  • AC6 was shown to be the key mediator of cholera enterotoxin-induced CFTR activation.

Conclusions:

  • Adenylate cyclase isoform 6 (AC6) is the elusive enzyme responsible for the pathological activation of the CFTR channel in cholera.
  • Targeting the AC6-CFTR interaction presents a promising new therapeutic strategy for treating cholera and related diarrheal diseases.

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