Transport proteins NHA1 and NHA2 are essential for survival, but have distinct transport modalities

Chintapalli, V. R., Kato, A., Henderson, L., Hirata, T., Woods, D. J., Overend, G., Davies, S. A. , Romero, M. F. and Dow, J. A. T. (2015) Transport proteins NHA1 and NHA2 are essential for survival, but have distinct transport modalities. Proceedings of the National Academy of Sciences of the United States of America, 112(37), pp. 11720-11725. (doi:10.1073/pnas.1508031112) (PMID:26324901) (PMCID:PMC4577160)

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Abstract

The cation/proton antiporter (CPA) family includes the well-known sodium/proton exchanger (NHE; SLC9A) family of Na+/H+ exchangers, and the more recently discovered and less well understood CPA2s (SLC9B), found widely in living organisms. In Drosophila, as in humans, they are represented by two genes, Nha1 (Slc9b1) and Nha2 (Slc9b2), which are enriched and functionally significant in renal tubules. The importance of their role in organismal survival has not been investigated in animals, however. Here we show that single RNAi knockdowns of either Nha1 or Nha2 reduce survival and in combination are lethal. Knockdown of either gene alone results in up-regulation of the other, suggesting functional complementation of the two genes. Under salt stress, knockdown of either gene decreases survival, demonstrating a key role for the CPA2 family in ion homeostasis. This is specific to Na+ stress; survival on K+ intoxication is not affected by sodium/hydrogen antiporter (NHA) knockdown. A direct functional assay in Xenopus oocytes shows that Nha2 acts as a Na+/H+ exchanger. In contrast, Nha1 expressed in Xenopus oocytes shows strong Cl− conductance and acts as a H+-Cl− cotransporter. The activity of Nha1 is inhibited by chloride-binding competitors 4,4′-diiso-thiocyano-2,2′-disulfonic acid stilbene and 4,4′-dibenzamido-2,2′-stilbenedisulphonate. Salt stress induces a massive up-regulation of NHA gene expression not in the major osmoregulatory tissues of the alimentary canal, but in the crop, cuticle, and associated tissues. Thus, it is necessary to revise the classical view of the coordination of different tissues in the coordination of the response to osmoregulatory stress.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dow, Professor Julian and Henderson, Ms Louise and Davies, Professor Shireen and Chintapalli, Dr Venkateswara and Overend, Dr Gayle
Authors: Chintapalli, V. R., Kato, A., Henderson, L., Hirata, T., Woods, D. J., Overend, G., Davies, S. A., Romero, M. F., and Dow, J. A. T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Copyright Holders:Copyright © 2015 National Academy of Sciences
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 112(37):11720-11725
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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