Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.3.2.19 (
ubiquitin-protein ligase
)
799
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background
Nedd4-2
is an E3
ubiquitin-protein ligase
that associates with transport proteins, causing their ubiquitylation, and then internalization and degradation. Previous research has suggested a correlation between
Nedd4-2
and BP. In this study, we explored the effect of intercalated cell (IC)
Nedd4-2
gene ablation on IC transporter abundance and function and on BP.
Methods
We generated IC
Nedd4-2
knockout mice using Cre-lox technology and produced global pendrin/
Nedd4-2
null mice by breeding global
Nedd4-2
null (
Nedd4-2
-/-
) mice with global pendrin null (
Slc26a4
-/-
) mice. Mice ate a diet with 1%-4% NaCl; BP was measured by tail cuff and radiotelemetry. We measured transepithelial transport of Cl
-
and total CO
2
and transepithelial voltage in cortical collecting ducts perfused
in vitro
Transporter
abundance was detected with immunoblots, immunohistochemistry, and immunogold cytochemistry.
Results
IC
Nedd4-2
gene ablation markedly increased electroneutral Cl
-
/HCO
3
-
exchange in the cortical collecting duct, although benzamil-, thiazide-, and bafilomycin-sensitive ion flux changed very little. IC
Nedd4-2
gene ablation did not increase the abundance of type B IC transporters, such as AE4 (
Slc4a9
), H
+
-ATPase, barttin, or the Na
+
-dependent Cl
-
/HCO
3
-
exchanger (
Slc4a8
). However, IC
Nedd4-2
gene ablation increased CIC-5 total protein abundance, apical plasma membrane pendrin abundance, and the ratio of pendrin expression on the apical membrane to the cytoplasm. IC
Nedd4-2
gene ablation increased BP by approximately 10 mm Hg. Moreover, pendrin gene ablation eliminated the increase in BP observed in global
Nedd4-2
knockout mice.
Conclusions
IC
Nedd4-2
regulates Cl
-
/HCO
3
-
exchange in ICs.,
Nedd4-2
gene ablation increases BP in part through its action in these cells.
...
PMID:The Role of Intercalated Cell
Nedd4-2
in BP Regulation, Ion Transport, and Transporter Expression. 2977 87
