XB-ART-498Proc Natl Acad Sci U S A. April 11, 2006; 103 (15): 5817-22.
Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels.
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.
PubMed ID: 16585520
PMC ID: PMC1458656
Article link: Proc Natl Acad Sci U S A.
Grant support: DK54354 NIDDK NIH HHS , DK65161 NIDDK NIH HHS , DK66883 NIDDK NIH HHS , HD043245 NICHD NIH HHS , F32 DK066883 NIDDK NIH HHS , R01 DK065161 NIDDK NIH HHS , DK66883 NIDDK NIH HHS , F32 DK066883 NIDDK NIH HHS , R56 DK065161 NIDDK NIH HHS , DK65161 NIDDK NIH HHS , R01 DK054354 NIDDK NIH HHS , K12 HD043245 NICHD NIH HHS , DK54354 NIDDK NIH HHS , HD043245 NICHD NIH HHS
Genes referenced: hsp70 hspa1l hspa8