Helicobacter pylori infection impairs chaperone-assisted maturation of Na,K-ATPase in gastric epithelium.

Helicobacter pylori infection impairs chaperone-assisted maturation of Na,K-ATPase in gastric epithelium. Am J Physiol Gastrointest Liver Physiol. 2020 Mar 16;: Authors: Marcus EA, Tokhtaeva E, Jimenez JL, Wen Y, Naini BV, Heard AN, Kim S, Capri J, Cohn W, Whitelegge JP, Vagin O Abstract Helicobacter pylori infection always induces gastritis, which may progress to ulcer disease or cancer. The mechanisms underlying mucosal injury by the bacteria are incompletely understood. Here we identify a novel pathway for H. pylori-induced gastric injury, the impairment of maturation of the essential transport enzyme and cell adhesion molecule, Na,K-ATPase. The Na,K-ATPase is comprised of α and β subunits that assemble in the ER prior to trafficking to the plasma membrane. Attachment of H. pylori to gastric epithelial cells increased Na,K-ATPase ubiquitylation, decreased its surface and total levels, and impaired ion balance. H. pylori did not alter degradation of plasmalemma-resident Na,K-ATPase subunits or their mRNA levels. Infection decreased association of α and β subunits with ER chaperone BiP and impaired assembly of α-β heterodimers as was revealed by quantitative mass spectrometry and immunoblotting of immunoprecipitated complexes. Total level of BiP was not altered, and the decrease in interaction with BiP was not observed for other BiP client proteins. H. pylori-induced decrease in Na,K-ATPase was prevented by BiP over-expression...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research