Traditional and emerging roles for the SLC9 Na+/H+ exchangers
@article{Fuster2013TraditionalAE, title={Traditional and emerging roles for the SLC9 Na+/H+ exchangers}, author={Daniel G. Fuster and R. Todd Alexander}, journal={Pfl{\"u}gers Archiv - European Journal of Physiology}, year={2013}, volume={466}, pages={61-76} }
The SLC9 gene family encodes Na+/H+ exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi, and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [22, 46, 128]. The SLC9 gene family (solute carrier classification of transporters: www…
136 Citations
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This review presents and discusses the pioneering original work as well as the current state-of-the-art research on mammalian NHEs, the solute carrier (SLC) 9 family, and provides a comprehensive view of core knowledge and recent insights into each family member.
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A summary of the structure, function and regulation of expression of the SLC9B subfamily members, focusing primarily on the better-studied SLC8B paralog, NHA2, is presented and the potential of these members as drug targets is reviewed.
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The present review described the basic biology of NHEs and highlighted their physiological and pathological effects in the liver.
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Several aspects of prokaryotic Na+/H+ exchanger structure and function are reviewed, discussing the similarities and differences between different transporters, with a focus on the CPA and IT exchangers.
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It is shown that single RNAi knockdowns of either Nha1 or Nha2 reduce survival and in combination are lethal, demonstrating a key role for the CPA2 family in ion homeostasis.
Structure, mechanism and lipid-mediated remodeling of the mammalian Na+/H+ exchanger NHA2
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The cryo-EM structures of bison NHA2 in detergent and in nanodiscs are reported, and it is proposed that the additional N-terminal helix has evolved as a lipid-mediated remodeling switch for the regulation of N HA2 activity.
Na+/H+ Exchangers Are Required for the Development and Function of Vertebrate Mucociliary Epithelia
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A requirement for NHEs in vertebrate mucociliary epithelia is revealed and NHE activity is linked to cilia formation and function in differentiating MCCs and the results provide an entry point for the understanding of the contribution of N HEs to signaling, development, and pathogenesis in the human respiratory tract.
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It is shown that one can switch the antiport activity of the bacterial Na+/H+ antiporter NapA from being electrogenic to electroneutral by the mutation of a single lysine residue (K305).
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The involvement of Na+/H+ exchangers (NHE) belonging to the SLC9 family and/or voltage-gated proton channels (HVCN1) in sperm capacitation and the acrosome reaction is discussed.
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Cryogenic electron microscopy of NHE isoform 9 from Equus caballus reveals the conserved architecture of the NHE ion‐binding site, their elevator‐like structural transitions, the functional implications of autism disease mutations and the role of phosphoinositide lipids to promote homodimerization that, together, have important physiological ramifications.
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