The endoplasmic reticulum-associated degradation of the epithelial sodium channel requires a unique complement of molecular chaperones.

Molecular Biology of the Cell
Teresa M BuckJ L Brodsky

Abstract

The epithelial sodium channel (ENaC) is composed of a single copy of an alpha-, beta-, and gamma-subunit and plays an essential role in water and salt balance. Because ENaC assembles inefficiently after its insertion into the ER, a substantial percentage of each subunit is targeted for ER-associated degradation (ERAD). To define how the ENaC subunits are selected for degradation, we developed novel yeast expression systems for each ENaC subunit. Data from this analysis suggested that ENaC subunits display folding defects in more than one compartment and that subunit turnover might require a unique group of factors. Consistent with this hypothesis, yeast lacking the lumenal Hsp40s, Jem1 and Scj1, exhibited defects in ENaC degradation, whereas BiP function was dispensable. We also discovered that Jem1 and Scj1 assist in ENaC ubiquitination, and overexpression of ERdj3 and ERdj4, two lumenal mammalian Hsp40s, increased the proteasome-mediated degradation of ENaC in vertebrate cells. Our data indicate that Hsp40s can act independently of Hsp70 to select substrates for ERAD.

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Citations

Oct 26, 2010·Pflügers Archiv : European journal of physiology·Daniela Rotin, Olivier Staub
Oct 27, 2011·The Journal of Biological Chemistry·Patrick G NeedhamJeffrey L Brodsky
May 13, 2010·The Journal of Biological Chemistry·James K Bubien
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Methods Mentioned

BETA
protein folding
ubiquitination
PCR
glycosylation

Software Mentioned

Image Gauge
Kodak
pClamp
QED Imaging

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