Functional and molecular characterization of the human neutral
solute channel aquaporin 9.
Tsukaguchi, Hiroyasu, Stanislawa Weremowicz, Cynthia C. Morton and
Matthias A. Hediger.
#Renal Division, Department of Medicine, and *Departments of
Pathology and Obstetrics, Gynecology and Reproductive Biology,
Brigham & Women's Hospital and Harvard Medical School, Boston, MA
02115, and **Department of Biological Chemistry and Molecular
Pharmacology, Harvard Medical School, Boston, MA 02115.
APStracts 6:0116F, 1999.
In metabolically active cells, the coordinated transport of water and
solutes is important for maintaining osmotic homeostasis. We recently
identified a broad selective-neutral solute channel, AQP9, from rat
liver which allows the passage of a wide variety of water and neutral
solutes (Tsukaguchi et al. J. Biol. Chem. 273, 24737-24743, 1998). A
human homologue (hAQP9) with 76% amino acid sequence identity to rat
AQP9 (rAQP9) was described but its permeability was found to be
restricted to water and urea (Ishibashi et al., Biochem. Biophys.
Res. Commun. 244, 268-274, 1998). Here we report a reevaluation of
the functional characteristics of hAQP9, its tissue distribution, the
structure of its gene and its chromosomal localization. When
expressed in Xenopus oocytes, hAQP9 allowed passage of a wide variety
of non-charged solutes, including carbamides, polyols, purines and
pyrimidines, in a phloretin- and mercurial-sensitive manner. These
functional characteristics are similar to those of rAQP9. Based on
Northern blot analysis, both _rat and human AQP9 are abundantly
expressed in liver, whereas, in contrast to rAQP9, hAQP9 is also
expressed in peripheral leukocytes and in tissues that accumulate
leukocytes, such as lung, spleen, and bone marrow. The human AQP9
gene is composed of 6 exons and 5 introns distributed over
approximately [sim]25 kilobases. The gene organization is strikingly
similar to that reported for human AQP3 and AQP7, suggesting their
evolution from a common ancestral gene. The promoter region contains
putative tonicity and glucocorticoid responsive elements, suggesting
that AQP9 may be regulated by osmolality and catabolism. Fluorescence
in situ hybridization assigned its locus to chromosome 15 q22.1-22.2.
Our data show that hAQP9 serves as a promiscuous solute channel
expressed in both liver and peripheral leukocytes where it is ideally
suited to transport of metabolites and/or nutrients into and out of
these cells.
Received 1 April 1999; accepted in final form 4 June 1999.
APS Manuscript Number F088-9.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 25 June 1999