Structure, function and regulation of the Na^+/H^+ exchanger

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Mammalian Na^+/H^+ exchanger (NHE) is a ubiquitous plasma membrane transporter that regulates intracellular pH and cell volume, and epithelial absorption of Na^+ and bicarbonate in kidney and intestine. During 2 years, we studied about structure-function and regulatory mechanism of NHE, and obtained following results.1. We discovered that one of exchanger-binding proteins, calcineurin-homologous protein (CHP) is an essential cofactor for physiological activity of multiple exchanger isoforms (JBC, 2001, in press).2. Based on cysteine accessibility analysis, we presented a novel topology model of NHE1 (JBC, 2000).3. We identified critical amino acid residues important for plasma membrane expression of NHE1 and found that second mutations at several positions rescued surface expression of NHE1 (FEBS letters, 2000).4. We found that Li^+ ion is an activator of NHE isoforms NHE1 and NHE2, and tyrosine kinase may be involved in this activation process (Pflugers Archiv. 2000).5. We found that the extracellular loop is responsible for different volume sensitivity of NHE1 and NHE2 (submitted).