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Updated: Jun 2, 2026
12:15
In Vitro Polymerization of F-actin on Early Endosomes
Published on: August 28, 2017
Cortical actin binding protein cortactin mediates ENaC activity via Arp2/3 complex
Daria V Ilatovskaya1, Tengis S Pavlov, Vladislav Levchenko
1Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
Summary
Cortactin regulates epithelial sodium channel (ENaC) activity in the kidney by interacting with its subunits and influencing channel open probability. This interaction is mediated by the Arp2/3 complex, impacting sodium reabsorption.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Physiology
Background:
- Epithelial sodium channel (ENaC) activity is crucial for sodium balance and is modulated by the cortical cytoskeleton.
- Cortactin, a protein associated with the actin cytoskeleton, is found in kidney epithelial cells.
Purpose of the Study:
- To investigate the role of cortactin in regulating ENaC activity in the kidney.
- To elucidate the molecular mechanism by which cortactin affects ENaC function.
Main Methods:
- Patch-clamp electrophysiology to measure ENaC activity.
- Biotinylation and single-channel analysis to assess channel function.
- Coimmunoprecipitation to detect protein interactions.
- Cortactin mutants and Arp2/3 complex inhibitors were used to probe the mechanism.
Main Results:
- Cortactin is highly expressed in kidney cortical collecting duct cells and co-localizes with ENaC.
- Coexpression of cortactin with ENaC reduced ENaC activity by decreasing channel open probability.
- Cortactin knockdown increased ENaC activity and sodium reabsorption.
- Cortactin directly interacts with ENaC subunits, and its effect on ENaC activity depends on Arp2/3 complex binding.
Conclusions:
- Cortactin plays a significant role in regulating ENaC activity in kidney principal cells.
- The Arp2/3 complex is essential for cortactin's mechanism of ENaC regulation.
- Cortactin influences ENaC function through cytoskeletal interactions, impacting sodium homeostasis.
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