Modulation of H+,K+-ATPase activity by the molecular chaperone ERp57 highly expressed in gastric parietal cells

• ERp57 is abundantly expressed in the apical membrane of gastric parietal cells.
• ERp57 positively regulates H+,K+-ATPase activity apart from its chaperoning function.
• ERp57 has no effect on Na+,K+-ATPase activity.

ERp57 is a ubiquitous ER chaperone that has disulfide isomerase activity. Here, we found that both ERp57 and gastric H+,K+-ATPase are expressed in a sample derived from the apical canalicular membranes of parietal cells. Overexpression of ERp57 in HEK293 cells stably expressing H+,K+-ATPase significantly increased the ATPase activity without changing the expression level of H+,K+-ATPase. Interestingly, overexpression of a catalytically inactive mutant of ERp57 (C57S/C60S/C406S/C409S) in the cells also increased H+,K+-ATPase activity. In contrast, knockdown of endogenous ERp57 in H+,K+-ATPase-expressing cells significantly decreased ATPase activity without changing the expression level of H+,K+-ATPase. Overexpression and knockdown of ERp57 had no significant effect on the expression and function of Na+,K+-ATPase. These results suggest that ERp57 positively regulates H+,K+-ATPase activity apart from its chaperoning function.

Structured summary of protein interactionsERp57physically interacts with alphaHK by anti bait coimmunoprecipitation (View interaction)