Small heat shock protein αA-crystallin regulates epithelial sodium channel expression

Ossama B. Kashlan, Gunhild M. Mueller, Mohammad Z. Qamar, Paul A. Poland, Annette Ahner, Ronald C. Rubenstein, Rebecca P. Hughey, Jeffrey L. Brodsky, Thomas R. Kleyman

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Integral membrane proteins are synthesized on the cytoplasmic face of the endoplasmic reticulum (ER). After being translocated or inserted into the ER, they fold and undergo posttranslational modifications. Within the ER, proteins are also subjected to quality control checkpoints, during which misfolded proteins may be degraded by proteasomes via a process known as ER-associated degradation. Molecular chaperones, including the small heat shock protein αA-crystallin, have recently been shown to play a role in this process. We have now found that αA-crystallin is expressed in cultured mouse collecting duct cells, where apical Na+ transport is mediated by epithelial Na+ channels (ENaC). ENaC-mediated Na+ currents in Xenopus oocytes were reduced by co-expression of αA-crystallin. This reduction in ENaC activity reflected a decrease in the number of channels expressed at the cell surface. Furthermore, we observed that the rate of ENaC delivery to the cell surface of Xenopus oocytes was significantly reduced by co-expression of αA-crystallin, whereas the rate of channel retrieval remained unchanged. We also observed that αA-crystallin and ENaC coimmunoprecipitate. These data are consistent with the hypothesis that small heat shock proteins recognize ENaC subunits at ER quality control checkpoints and can target ENaC subunits for ER-associated degradation.

Original languageEnglish
Pages (from-to)28149-28156
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number38
DOIs
StatePublished - Sep 21 2007

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