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• W2051201900 abstract "Calcineurin B homologous proteins (CHP) are N-myristoylated, EF-hand Ca(2+)-binding proteins that regulate multiple cellular processes, including intracellular pH homeostasis. Previous work has shown that the heart-enriched isoform, CHP3, regulates the plasmalemmal Na(+)/H(+) exchanger NHE1 isoform by enhancing its rate of oligosaccharide maturation and exocytosis as well as its half-life and transport activity at the cell surface (Zaun, H. C., Shrier, A., and Orlowski, J. (2008) J. Biol. Chem. 283, 12456-12467). However, the molecular basis for this effect is not well understood. In this report, we investigated whether the N-myristoylation and Ca(2+)-binding domains of CHP3 are important elements for regulating NHE1. Mutation of residues essential for either N-myristoylation (G2A) or calcium binding (D123A) did not prevent the interaction of CHP3 with NHE1, although the D123A mutant no longer showed elevated binding to NHE1 in the presence of Ca(2+) when assessed using in vitro binding assays. Disruption of either site also did not impair the ability of CHP3 to stimulate the biosynthetic processing and trafficking of NHE1 to the plasma membrane nor did it affect the H(+) sensitivity of the exchanger. However, they did significantly reduce the cell surface half-life and near maximal transport velocity of NHE1 to a similar extent. Simultaneous mutation of both sites (G2A/D123A) gave results identical to the individual substitutions. This finding suggests that both domains in CHP3 are interdependent and may function cooperatively as a Ca(2+)-myristoyl switch mechanism to selectively stabilize the NHE1·CHP3 complex at the cell surface in a conformation that promotes optimal transport activity." @default.
• W2051201900 created "2016-06-24" @default.
• W2051201900 creator A5000377064 @default.
• W2051201900 creator A5081149858 @default.
• W2051201900 creator A5081564951 @default.
• W2051201900 date "2012-10-01" @default.
• W2051201900 modified "2023-10-05" @default.
• W2051201900 title "N-Myristoylation and Ca2+ Binding of Calcineurin B Homologous Protein CHP3 Are Required to Enhance Na+/H+ Exchanger NHE1 Half-life and Activity at the Plasma Membrane" @default.
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• W2051201900 doi "https://doi.org/10.1074/jbc.m112.394700" @default.
• W2051201900 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3481291" @default.
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• W2051201900 hasPublicationYear "2012" @default.
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