<i>Salty dog</i>, an SLC5 symporter, modulates<i>Drosophila</i>response to salt stress

Stergiopoulos, K.; Cabrero, Pablo; Davies, Shireen-A.; Dow, Julian A. T.

doi:10.1152/physiolgenomics.90360.2008

Cited by 72 publications

(73 citation statements)

References 45 publications

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“…Accordingly, we exposed the flies to salt stress. We and others have previously shown that a diet supplemented with 4% wt/vol NaCl is lethal to wild type (WT) Drosophila over several days (25). When WT flies were compared with either Nha1 or Nha2 knockdowns, or Nha1/Nha2 double knockdown escapers, it was obvious that NHA knockdowns reduced survival time on a NaCl diet (Fig.…”

Section: Resultsmentioning

confidence: 87%

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

Chintapalli

Kato

Henderson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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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.The NHA Gene Family Ionic homeostasis is essential for life and requires a significant fraction of an organism's total energy budget. Primary ion-motive ATPases provide electrochemical ion gradients to drive an array of channels, cotransporters, and antiporters. The cation/proton antiporter (CPA) family is ubiquitous and best known for the NHE, or CPA1, branch exemplified by the classical Na + /H + exchanger NHE1 (1, 2), which is a target for the potassium-sparing diuretic amiloride in the treatment of hypertension and congestive heart failure. More recently discovered are the sodium/hydrogen antiporters (NHAs), a subbranch of the CPA2 family, which is much less well understood (3, 4). Originally studied in bacteria, yeast, and plants (5, 6), this subbranch in humans includes two NHA genes in tandem: NHA1 (SLC9B1), which is testis-specific, and NHA2 (SLC9B2), which is ubiquitous (7,8).In osteoclasts, NHA2 colocalizes with the V-ATPase a3 subunit and the lysosomal marker LAMP2 (9), and resides in the plasma membrane of Madin-Darby canine kidney (MDCK) cells (7). In the pancreas, NHA2 is necessary for insulin secretion but localizes not to insulin-containing vesicles, but rather to transferrin-positive endocytic vesicles (4, 10). NHA2 also has been linked to hypertension (8). Thus, NHAs are multifunctional proteins expressed in a wide range of ...

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Section: Resultsmentioning

confidence: 87%

“…Survival assays were performed as described previously (25). In brief, 7-d-old adult female flies were taken from their vials, kept in empty vials for 4 h to ensure prompt subsequent feeding, and then transferred in groups of 20-30 to vials containing a normal diet supplemented with different concentrations of NaCl or KCl.…”

Section: Methodsmentioning

confidence: 99%

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

Chintapalli

Kato

Henderson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Members of the immune induced molecule family are also highly induced. These transcripts have been found to be associated with the activation of Toll and JAK/STAT pathways of immunity (Kwon et al 2008) and with salt-stressed flies (Stergiopoulos et al 2009).…”

Section: Ex1mentioning

confidence: 99%

Role of Elongator Subunit Elp3 in Drosophila melanogaster Larval Development and Immunity

et al. 2011

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The Elongator complex has been implicated in several cellular processes, including gene expression and tRNA modification. We investigated the biological importance of the Elp3 gene in Drosophila melanogaster. Deletion of Elp3 results in larval lethality at the pupal stage. During early development, larval growth is dramatically impaired, with progression to the third instar delayed for $24 hr, and pupariation occurring only at day 14 after egg laying. Melanotic nodules appear after 4 days. Microarray analysis shows that stress response genes are induced and ecdysone-induced transcription factors are severely repressed in the mutant. Interestingly, the phenotypes of Elp3 flies are similar to those of flies lacking the domino gene, encoding a SWI/SNF-like ATP-dependent chromatin-remodeling enzyme. Indeed, the gene expression profiles of these mutants are also remarkably similar. Together, these data demonstrate that Drosophila Elp3 is essential for viability, normal development, and hematopoiesis and suggest a functional overlap with the chromatin remodeler Domino.

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“…The fruit fly Drosophila is also capable of precise haemolymph osmoregulation in response to addition of 300mmoll -1 sucrose or NaCl to the diet (Pierce et al, 1999), or during dehydration and rehydration (Albers and Bradley, 2004). Most genes that are upregulated or downregulated by salt stress are highly enriched in the Malpighian tubules and/or the hindgut, suggesting that these tissues play major roles in the response to salt stress (Stergiopoulos et al, 2008). There is a robust increase in carbohydrate metabolism during salt stress, and expression of the GLUT4/8-like sugar transporter gene CG6484 is elevated 2700-fold in the midgut, relative to whole flies, whereas expression of the putative sodium/halide symporter gene salty dog (CG2196) is 7000-fold higher in the Malpighian tubules than in whole flies (Stergiopoulos et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Most genes that are upregulated or downregulated by salt stress are highly enriched in the Malpighian tubules and/or the hindgut, suggesting that these tissues play major roles in the response to salt stress (Stergiopoulos et al, 2008). There is a robust increase in carbohydrate metabolism during salt stress, and expression of the GLUT4/8-like sugar transporter gene CG6484 is elevated 2700-fold in the midgut, relative to whole flies, whereas expression of the putative sodium/halide symporter gene salty dog (CG2196) is 7000-fold higher in the Malpighian tubules than in whole flies (Stergiopoulos et al, 2008). In addition, two proteins encoded by the inebriated (ine) gene have been implicated in osmolyte transport within the Malpighian tubule and hindgut.…”

Section: Introductionmentioning

confidence: 99%

Phenotypic plasticity in response to dietary salt stress: Na+ and K+ transport by the gut ofDrosophila melanogasterlarvae

Naikkhwah

O’Donnell

2012

Journal of Experimental Biology

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SUMMARYDrosophila provides a useful model system for studies of the mechanisms involved in regulation of internal ion levels in response to variations in dietary salt load. This study assessed whether alterations in Na + and K + transport by the gut of larval D. melanogaster reared on salt-rich diets contribute to haemolymph ionoregulation. Na + and K + fluxes across the isolated guts of third instar larvae reared on control or salt-rich diets were measured using the scanning ion-selective electrode technique (SIET). K + absorption across the anterior portion of the posterior midgut of larvae reared on diet in which the concentration of KCl was increased 0.4moll -1 above that in the control diet was reduced eightfold relative to the same gut segment of larvae reared on the control diet. There was also an increase in the magnitude and extent of K + secretion across the posterior half of the posterior midgut. Na + was absorbed across the ileum of larvae reared on the control diet, but was secreted across the ileum of larvae reared on diet in which the concentration of NaCl was increased 0.4moll -1 above that in the control diet. There was also a small reduction in the extent of Na + absorption across the middle midgut of larvae reared on the NaCl-rich diet. The results indicate considerable phenotypic plasticity with respect to K + and Na + transport by the gut epithelia of larval D. melanogaster. SIET measurements of K + and Na + fluxes along the length of the gut show that ion transport mechanisms of the gut are reconfigured during salt stress so that there are reductions in K + and Na + absorption and increases in K + and Na + secretion. Together with previously described changes in salt secretion by the Malpighian tubules, these changes contribute to haemolymph ionoregulation.

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Salty dog, an SLC5 symporter, modulatesDrosophilaresponse to salt stress

Cited by 72 publications

References 45 publications

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

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

Role of Elongator Subunit Elp3 in Drosophila melanogaster Larval Development and Immunity

Phenotypic plasticity in response to dietary salt stress: Na+ and K+ transport by the gut ofDrosophila melanogasterlarvae

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