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A mechanism for the activation of the Na/H exchanger NHE‐1 by cytoplasmic acidification and mitogens
Author(s) -
Lacroix Jérôme,
Poët Mallorie,
Maehrel Céline,
Counillon Laurent
Publication year - 2004
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400035
Subject(s) - intracellular ph , intracellular , transporter , sodium–hydrogen antiporter , cytoplasm , biophysics , chemistry , microbiology and biotechnology , biochemistry , mechanism (biology) , proton , biology , sodium , gene , physics , organic chemistry , quantum mechanics
Eukaryotic cells constantly have to fight against internal acidification. In mammals, this task is mainly performed by the ubiquitously expressed electroneutral Na + /H + exchanger NHE‐1, which activates in a cooperative manner when cells become acidic. Despite its biological importance, the mechanism of this activation is still poorly understood, the most commonly accepted hypothesis being the existence of a proton‐sensor site on the internal face of the transporter. This work uncovers mutations that lead to a nonallosteric form of the exchanger and demonstrates that NHE‐1 activation is best described by a Monod–Wyman–Changeux concerted mechanism for a dimeric transporter. During intracellular acidification, a low‐affinity form of NHE‐1 is converted into a form possessing a higher affinity for intracellular protons, with no requirement for an additional proton‐sensor site on the protein. This new mechanism also explains the activation of the exchanger by growth signals, which shift the equilibrium towards the high‐affinity form.