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J. Biol. Chem., Vol. 276, Issue 20, 17387-17394, May 18, 2001
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From the Department of Physiology, McGill University,
Montréal, Québec H3G 1Y6, Canada
The luminal pH of organelles along the secretory
and endocytic pathways of mammalian cells is acidic and tightly
regulated, with the [H+] varying up to 100-fold
between compartments. Steady-state organellar pH is thought to reflect
a balance between the rates of H+ pumping by the
vacuolar-type H+-ATPase and H+ efflux through
ill-defined pathways. Here, we describe the cloning of a novel gene
(NHE7) in humans that is homologous to
Na+/H+ exchangers, is ubiquitously expressed,
and localizes predominantly to the trans-Golgi network.
Significantly, NHE7 mediates the influx of Na+ or
K+ in exchange for H+. The activity of NHE7 was
also found to be relatively insensitive to inhibition by amiloride but
could be antagonized by the analogue benzamil and the unrelated
compound quinine. Thus, NHE7 displays unique functional and
pharmacological properties and may play an important role in
maintaining cation homeostasis of this important organelle.
Molecular Cloning and Characterization of a Novel
(Na+,K+)/H+ Exchanger Localized to
the trans-Golgi Network*
*
This work was supported by the Canadian Institutes for
Health Research.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Physiology,
McGill University, McIntyre Medical Sciences Bldg., 3655 Promenade
Sir-William-Osler, Montreal, Quebec H3G 1Y6, Canada. Tel.:
514-398-8335; Fax: 514-398-7452; E-mail: orlowski@med.mcgill.ca.
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