期刊
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
卷 294, 期 5, 页码 F1157-F1165出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00339.2007
关键词
sodium transport; collecting duct; hypertension
资金
- NHLBI NIH HHS [HL-71664, R01 HL071664-05, R01 HL071664] Funding Source: Medline
We previously reported the existence of multiple isoforms of human Nedd4-2 (Am J Physiol Renal Physiol 285: F916-F929, 2003). When overexpressed in M-1 collecting duct epithelia, full-length Nedd4-2 (Nedd4-2), Nedd4-2 lacking the NH2-terminal C2 domain (Nedd4-2 Delta C2), and Nedd4-2 lacking WW domains 2 and 3 (Nedd4-2 Delta WW2,3) variably reduce benzamil-sensitive Na+ transport. We investigated the effect of each of the Nedd4-2 isoforms on cell surface expression and ubiquitination of ENaC subunits. We find that alpha ENaC when transfected alone or with beta and gamma ENaC is expressed at the cell surface and this membrane expression is variably reduced by coexpression with each of the Nedd4-2 isoforms. Nedd4-2 reduces the half-life of ENaC subunits and enhances the ubiquitination of alpha,beta, and gamma ENaC subunits when expressed alone or together suggesting that each subunit is a target for Nedd4-2-mediated ubiquitination. As has been reported recently, we confirm that the surface-expressed pool of ENaC is multi-ubiquitinated. Inhibitors of the proteasome increase ubiquitination of ENaC subunits and stimulate Na+ transport in M-1 cells consistent with a role for the ubiquitin-proteasome pathway in regulating Na+ transport in the collecting duct.
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