Molecular mechanism for regulaiton of ion transporter via lipid signaling and its structural basis

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Although plasma membrane ion transports are delicately controlled by many signals, its breakdown contributes to exacerbation of various diseases. In this research, we studied in details about the regulatory mechanism of mammalian Na+/H+ exchanger NHE1, which was unknown until now. We found that NHE1 is an ATP binding protein, and that NHE1 activity is maintained by direct binding of ATP. Furthermore, hormonal activation of NHE1 was found to occur by the switching mechanism between ATP and bioactive lipids (diacylglycerol, etc.) via lipid-interacting domain of NHE1. Moreover, activation of NHE1 was found to amplify the NFAT signaling via calcineurin which directly interacts with NHE1.