Differential Effects of Hsc70 and Hsp70 on the Intracellular Trafficking and Functional Expression of Epithelial Sodium Channels

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-04, Vol.103 (15), p.5817-5822
• Main Authors: Goldfarb, Samuel B., Kashlan, Ossama B., Watkins, Jeffrey N., Suaud, Laurence, Yan, Wusheng, Kleyman, Thomas R., Rubenstein, Ronald C.
• Format: Article
• Language: English
• Subjects: Animals; Biological Sciences; Cell Communication - physiology; Cell Membrane - physiology; Cellular biology; Cloning, Molecular; Complementary RNA; Electrophysiology; Endocytosis; Epithelial Sodium Channels; Epitopes; Exocytosis; Female; Gene expression; Gene Expression Regulation; HSC70 Heat-Shock Proteins - physiology; HSP70 Heat-Shock Proteins - physiology; Humans; Hypotheses; Ion channels; Membrane Potentials; Mice; Oocytes; Oocytes - physiology; P values; Physiological regulation; Proteins; Sodium; Sodium channels; Sodium Channels - genetics; Transfection; Xenopus
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0507903103

The members of the cytoplasmic 70-kDa heat shock protein family are involved in appropriate folding and trafficking of newly synthesized proteins in the cell. Hsc70, which is expressed constitutively, and Hsp70, the expression of which is stress- and heat shock-induced, are often considered to have similar cellular functions in this regard, but there are suggestions that the intracellular functions of these homologous but not identical proteins may differ. We tested the hypothesis that Hsc70 and Hsp70 would have differential effects on the expression of the epithelial sodium channel (ENaC). In Xenopus oocytes, overexpression of human Hsc70 decreased the functional (defined as amiloride-sensitive whole-oocyte current) and surface expression of murine ENaC (mENaC) in a concentration-dependent fashion. In contrast, coinjection of a moderate amount of Hsp70 cRNA (10 ng) increased the functional and surface expression of mENaC, whereas a higher amount of coinjected Hsp70 cRNA (30 ng) decreased mENaC functional and surface expression. The increase in mENaC functional expression with coinjection of 10 ng of Hsp70 cRNA was antagonized by the additional coinjection of Hsc70 cRNA in a concentration-dependent fashion. These data are consistent with Hsc70 and Hsp70 having differential and antagonistic effects with regard to the intracellular trafficking of mENaC in oocytes, which may have an impact on our understanding and potential treatment of diseases of aberrant ion channel trafficking.