Differential Assembly of Native ENaC Complexes Across Mouse Epithelial Tissues.
Arpita Bharadwaj1, Joshua Curry2, Xiao-Tong Su2
1Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239.
Kidney360
|June 15, 2026
Summary
The epithelial sodium channel (ENaC) has varied molecular organization across tissues. Endogenous tagging reveals distinct ENaC assembly and regulatory states in vivo.
Area of Science:
- Molecular biology
- Physiology
- Biochemistry
Background:
- The epithelial sodium channel (ENaC) is crucial for sodium and fluid absorption in epithelia.
- Its in vivo molecular organization, assembly, and regulation are poorly understood due to low abundance and instability.
Purpose of the Study:
- To investigate the in vivo molecular organization and regulation of native epithelial sodium channel complexes.
- To overcome limitations in analyzing ENaC assembly and composition in native tissues.
Main Methods:
- Generated a knock-in mouse with a tagged epithelial sodium channel gamma subunit, preserving function.
- Analyzed native ENaC complexes from lung, kidney, and colon using advanced techniques like fluorescence-detection size-exclusion chromatography and mass spectrometry.
Main Results:
- The tagged gamma subunit confirmed normal ENaC function in vivo.
- Native ENaC complexes displayed tissue-specific differences in abundance and size.
- Proteomic analysis identified diverse regulatory proteins associated with ENaC, indicating multiple assembly states.
Conclusions:
- Epithelial sodium channel architecture is heterogeneous across different epithelial tissues.
- Endogenous tagging provides a powerful tool for direct molecular study of ENaC assembly and regulation in vivo.
