Nedd4 and Nedd4-2 are ubiquitin-protein ligases known to regulate a number of membrane proteins including receptors and ion transporters. Regulation of the epithelial Na+ channel by Nedd4 and Nedd4-2 is mediated via interactions between the PY motifs of the epithelial sodium channel subunits and the Nedd4/Nedd4-2 WW domains. This example serves as a model for the regulation of other PY motif-containing ion channels by Nedd4 and Nedd4-2. We found that the carboxyl termini of the six voltage-gated Na+ (Na-v) channels contain typical PY motifs (PPXY), and a further Na-v contains a PY motif variant (LPXY). Not only did we demonstrate by Far-Western analysis that Nedd4 and Nedd4-2 interact with the PY motif-containing Na-v channels, but we also showed that these channels have conserved WW domain binding specificity. We further showed that the carboxyl termini fusion proteins of one central nervous system and one peripheral nervous system-derived Na+ channel (Na(v)1.2 and Na(v)1.7, respectively) are readily ubiquitinated by Nedd4-2. In Xenopus oocytes, Nedd4-2 strongly inhibited the activities of all three Na(v)s (Na(v)1.2, Na(v)1.7, and Na(v)1.8) tested. Interestingly, Nedd4 suppressed the activity of Na(v)1.2 and Na(v)1.7 but was a poor inhibitor of Na(v)1.8. Our results provide evidence that Nedd4 and Nedd4-2 are likely to be key regulators of specific neuronal Na-v channels in vivo.
机构:
FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
DARGENT, B
;
PAILLART, C
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FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
PAILLART, C
;
CARLIER, E
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FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
CARLIER, E
;
ALCARAZ, G
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FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
ALCARAZ, G
;
MARTINEAUCLAIRE, MF
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FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
MARTINEAUCLAIRE, MF
;
COURAUD, F
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机构:
FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
机构:
FAC MED SECTEUR NORD MARSEILLE,CNRS,UA 1179,BIOCHIM LAB,BLVD PIERRE DRAMARD,F-13326 MARSEILLE 15,FRANCEFAC MED SECTEUR NORD MARSEILLE,CNRS,UA 1179,BIOCHIM LAB,BLVD PIERRE DRAMARD,F-13326 MARSEILLE 15,FRANCE
DARGENT, B
;
COURAUD, F
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机构:
FAC MED SECTEUR NORD MARSEILLE,CNRS,UA 1179,BIOCHIM LAB,BLVD PIERRE DRAMARD,F-13326 MARSEILLE 15,FRANCEFAC MED SECTEUR NORD MARSEILLE,CNRS,UA 1179,BIOCHIM LAB,BLVD PIERRE DRAMARD,F-13326 MARSEILLE 15,FRANCE
机构:
FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
DARGENT, B
;
PAILLART, C
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机构:
FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
PAILLART, C
;
CARLIER, E
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h-index: 0
机构:
FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
CARLIER, E
;
ALCARAZ, G
论文数: 0引用数: 0
h-index: 0
机构:
FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
ALCARAZ, G
;
MARTINEAUCLAIRE, MF
论文数: 0引用数: 0
h-index: 0
机构:
FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
MARTINEAUCLAIRE, MF
;
COURAUD, F
论文数: 0引用数: 0
h-index: 0
机构:
FAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCEFAC MED SECTOR NORD, INST JEAN ROCHE, CNRS, URA 1455, F-13916 MARSEILLE 20, FRANCE
机构:
FAC MED SECTEUR NORD MARSEILLE,CNRS,UA 1179,BIOCHIM LAB,BLVD PIERRE DRAMARD,F-13326 MARSEILLE 15,FRANCEFAC MED SECTEUR NORD MARSEILLE,CNRS,UA 1179,BIOCHIM LAB,BLVD PIERRE DRAMARD,F-13326 MARSEILLE 15,FRANCE
DARGENT, B
;
COURAUD, F
论文数: 0引用数: 0
h-index: 0
机构:
FAC MED SECTEUR NORD MARSEILLE,CNRS,UA 1179,BIOCHIM LAB,BLVD PIERRE DRAMARD,F-13326 MARSEILLE 15,FRANCEFAC MED SECTEUR NORD MARSEILLE,CNRS,UA 1179,BIOCHIM LAB,BLVD PIERRE DRAMARD,F-13326 MARSEILLE 15,FRANCE