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Drosophila TRPM channel is essential for the control of extracellular magnesium levels.

Hofmann T, Chubanov V, Chen X, Dietz AS, Gudermann T, Montell C - PLoS ONE (2010)

Bottom Line: We generated mutations in trpm and found that this resulted in shortening of the Malpighian tubules.In contrast to all other Drosophila trp mutations, loss of trpm was essential for viability, as trpm mutations resulted in pupal lethality.Feeding high Mg2+ also resulted in elevated Mg2+ in the hemolymph, but had relatively little effect on cellular Mg2+.

View Article: PubMed Central - PubMed

Affiliation: Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Marburg, Germany.

ABSTRACT
The TRPM group of cation channels plays diverse roles ranging from sensory signaling to Mg2+ homeostasis. In most metazoan organisms the TRPM subfamily is comprised of multiple members, including eight in humans. However, the Drosophila TRPM subfamily is unusual in that it consists of a single member. Currently, the functional requirements for this channel have not been reported. Here, we found that the Drosophila TRPM protein was expressed in the fly counterpart of mammalian kidneys, the Malpighian tubules, which function in the removal of electrolytes and toxic components from the hemolymph. We generated mutations in trpm and found that this resulted in shortening of the Malpighian tubules. In contrast to all other Drosophila trp mutations, loss of trpm was essential for viability, as trpm mutations resulted in pupal lethality. Supplementation of the diet with a high concentration of Mg2+ exacerbated the phenotype, resulting in growth arrest during the larval period. Feeding high Mg2+ also resulted in elevated Mg2+ in the hemolymph, but had relatively little effect on cellular Mg2+. We conclude that loss of Drosophila trpm leads to hypermagnesemia due to a defect in removal of Mg2+ from the hemolymph. These data provide the first evidence for a role for a Drosophila TRP channel in Mg2+ homeostasis, and underscore a broad and evolutionarily conserved role for TRPM channels in Mg2+ homeostasis.

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Altered Malpighian tubule morphology in the trpm mutant.(A) Representative images of anterior tubule pairs microdissected from 3rd instar larvae. The approximate location of the different segment borders are indicated: cd  =  collecting duct, ms  =  main segment, ts  =  transitional segment, is  =  initial segment). (B) Cell numbers in the w1118 and trpm tubules. The tubules were fixed and stained with DAPI and the numbers of nuclei in each tubule/segment were tabulated. Error bars represent SEMs.
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pone-0010519-g004: Altered Malpighian tubule morphology in the trpm mutant.(A) Representative images of anterior tubule pairs microdissected from 3rd instar larvae. The approximate location of the different segment borders are indicated: cd  =  collecting duct, ms  =  main segment, ts  =  transitional segment, is  =  initial segment). (B) Cell numbers in the w1118 and trpm tubules. The tubules were fixed and stained with DAPI and the numbers of nuclei in each tubule/segment were tabulated. Error bars represent SEMs.

Mentions: We found that the length and morphology of the larval Malpighian tubules was affected in the trpm 3rd instar larvae. The anterior tubule pair was 30% shorter than wild-type and contained fewer cells (Figure 4A and B). This difference was restricted to the main segment and the lower segment, while the transitional segment, initial segment and posterior tubules were similar in length to wild-type (Figure 4A and B).


Drosophila TRPM channel is essential for the control of extracellular magnesium levels.

Hofmann T, Chubanov V, Chen X, Dietz AS, Gudermann T, Montell C - PLoS ONE (2010)

Altered Malpighian tubule morphology in the trpm mutant.(A) Representative images of anterior tubule pairs microdissected from 3rd instar larvae. The approximate location of the different segment borders are indicated: cd  =  collecting duct, ms  =  main segment, ts  =  transitional segment, is  =  initial segment). (B) Cell numbers in the w1118 and trpm tubules. The tubules were fixed and stained with DAPI and the numbers of nuclei in each tubule/segment were tabulated. Error bars represent SEMs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865541&req=5

pone-0010519-g004: Altered Malpighian tubule morphology in the trpm mutant.(A) Representative images of anterior tubule pairs microdissected from 3rd instar larvae. The approximate location of the different segment borders are indicated: cd  =  collecting duct, ms  =  main segment, ts  =  transitional segment, is  =  initial segment). (B) Cell numbers in the w1118 and trpm tubules. The tubules were fixed and stained with DAPI and the numbers of nuclei in each tubule/segment were tabulated. Error bars represent SEMs.
Mentions: We found that the length and morphology of the larval Malpighian tubules was affected in the trpm 3rd instar larvae. The anterior tubule pair was 30% shorter than wild-type and contained fewer cells (Figure 4A and B). This difference was restricted to the main segment and the lower segment, while the transitional segment, initial segment and posterior tubules were similar in length to wild-type (Figure 4A and B).

Bottom Line: We generated mutations in trpm and found that this resulted in shortening of the Malpighian tubules.In contrast to all other Drosophila trp mutations, loss of trpm was essential for viability, as trpm mutations resulted in pupal lethality.Feeding high Mg2+ also resulted in elevated Mg2+ in the hemolymph, but had relatively little effect on cellular Mg2+.

View Article: PubMed Central - PubMed

Affiliation: Institut für Pharmakologie und Toxikologie, Philipps-Universität Marburg, Marburg, Germany.

ABSTRACT
The TRPM group of cation channels plays diverse roles ranging from sensory signaling to Mg2+ homeostasis. In most metazoan organisms the TRPM subfamily is comprised of multiple members, including eight in humans. However, the Drosophila TRPM subfamily is unusual in that it consists of a single member. Currently, the functional requirements for this channel have not been reported. Here, we found that the Drosophila TRPM protein was expressed in the fly counterpart of mammalian kidneys, the Malpighian tubules, which function in the removal of electrolytes and toxic components from the hemolymph. We generated mutations in trpm and found that this resulted in shortening of the Malpighian tubules. In contrast to all other Drosophila trp mutations, loss of trpm was essential for viability, as trpm mutations resulted in pupal lethality. Supplementation of the diet with a high concentration of Mg2+ exacerbated the phenotype, resulting in growth arrest during the larval period. Feeding high Mg2+ also resulted in elevated Mg2+ in the hemolymph, but had relatively little effect on cellular Mg2+. We conclude that loss of Drosophila trpm leads to hypermagnesemia due to a defect in removal of Mg2+ from the hemolymph. These data provide the first evidence for a role for a Drosophila TRP channel in Mg2+ homeostasis, and underscore a broad and evolutionarily conserved role for TRPM channels in Mg2+ homeostasis.

Show MeSH
Related in: MedlinePlus