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PMID:8521520
| Citation |
Snyder, PM, Price, MP, McDonald, FJ, Adams, CM, Volk, KA, Zeiher, BG, Stokes, JB and Welsh, MJ (1995) Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel. Cell 83:969-78 |
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| Abstract |
Liddle's syndrome is an inherited form of hypertension caused by mutations that truncate the C-terminus of human epithelial Na+ channel (hENaC) subunits. Expression of truncated beta and gamma hENaC subunits increased Na+ current. However, truncation did not alter single-channel conductance or open state probability, suggesting there were more channels in the plasma membrane. Moreover, truncation of the C-terminus of the beta subunit increased apical cell-surface expression of hENaC in a renal epithelium. We identified a conserved motif in the C-terminus of all three subunits that, when mutated, reproduced the effect of Liddle's truncations. Further, both truncation of the C-terminus and mutation of the conserved C-terminal motif increased surface expression of chimeric proteins containing the C-terminus of beta hENaC. Thus, by deleting a conserved motif, Liddle's mutations increase the number of Na+ channels in the apical membrane, which increases renal Na+ absorption and creates a predisposition to hypertension. |
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| Keywords |
Amiloride/pharmacology; Amino Acid Sequence; Animals; Cell Line; Consensus Sequence; Dogs; Electric Conductivity; Epithelial Sodium Channel; Epithelium; Frameshift Mutation; Humans; Hypertension/genetics; Hypertension/metabolism; Hypertension/physiopathology; Ion Channel Gating/drug effects; Kidney/cytology; Kidney/metabolism; Kidney/physiopathology; Molecular Sequence Data; Oocytes; Patch-Clamp Techniques; Sequence Deletion/genetics; Sodium Channels/biosynthesis; Sodium Channels/genetics; Sodium Channels/metabolism; Syndrome; Xenopus |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
enables |
GO:0005272: sodium channel activity |
ECO:0000304: author statement supported by traceable reference used in manual assertion |
F |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0006814: sodium ion transport |
ECO:0000304: author statement supported by traceable reference used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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