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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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Related in: MedlinePlus

Schematic showing the changes in Mg2+ homeostasis in trpm mutant larvae.The upper and lower halves of the wild-type and trpm larvae depict the main net transport paths for Mg2+ upon feeding on a diet containing 1 mM or 30 mM Mg2+. The thicker red lines and the darker hue of the background redness over the hemolymph space and the Malpighian tubules represent the higher Mg2+ concentration/density in their respective compartments. The white fat body indicates low synthetic capacity. The blue outlines on the initial and transitional segments of the wild-type Malpighian tubules delineate the localization of the TRPM protein.
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pone-0010519-g006: Schematic showing the changes in Mg2+ homeostasis in trpm mutant larvae.The upper and lower halves of the wild-type and trpm larvae depict the main net transport paths for Mg2+ upon feeding on a diet containing 1 mM or 30 mM Mg2+. The thicker red lines and the darker hue of the background redness over the hemolymph space and the Malpighian tubules represent the higher Mg2+ concentration/density in their respective compartments. The white fat body indicates low synthetic capacity. The blue outlines on the initial and transitional segments of the wild-type Malpighian tubules delineate the localization of the TRPM protein.

Mentions: While high Mg2+ largely enhanced the severity of the trpm larval growth phenotype, it appeared that supplementation of Mg2+ exclusively during the late-stage of larval development partially suppressed the biosynthetic defects in the fat body. In support of this conclusion, the protein content was much higher in larvae fed high Mg2+ on day 3 only, than in larvae maintained continuously on food with normal levels of Mg2+. These larvae, in contrast to larvae kept continuously on low Mg2+, displayed nearly normal hemolymph proteins. We propose that during early larval development when most larval growth is taking place, high Mg2+ in the diet is deleterious to trpm larvae because the hypermagnesemia suppresses feeding behavior and growth of tissues such as the fat bodies, which is a prerequisite for anabolic function. However, once morphogenesis and tissue growth is largely complete, as in late stage larvae, the high Mg2+ may contribute to Mg2+ resorption in tissues such as the fat bodies (Figure 6), thereby promoting biosynthetic function.


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)

Schematic showing the changes in Mg2+ homeostasis in trpm mutant larvae.The upper and lower halves of the wild-type and trpm larvae depict the main net transport paths for Mg2+ upon feeding on a diet containing 1 mM or 30 mM Mg2+. The thicker red lines and the darker hue of the background redness over the hemolymph space and the Malpighian tubules represent the higher Mg2+ concentration/density in their respective compartments. The white fat body indicates low synthetic capacity. The blue outlines on the initial and transitional segments of the wild-type Malpighian tubules delineate the localization of the TRPM protein.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0010519-g006: Schematic showing the changes in Mg2+ homeostasis in trpm mutant larvae.The upper and lower halves of the wild-type and trpm larvae depict the main net transport paths for Mg2+ upon feeding on a diet containing 1 mM or 30 mM Mg2+. The thicker red lines and the darker hue of the background redness over the hemolymph space and the Malpighian tubules represent the higher Mg2+ concentration/density in their respective compartments. The white fat body indicates low synthetic capacity. The blue outlines on the initial and transitional segments of the wild-type Malpighian tubules delineate the localization of the TRPM protein.
Mentions: While high Mg2+ largely enhanced the severity of the trpm larval growth phenotype, it appeared that supplementation of Mg2+ exclusively during the late-stage of larval development partially suppressed the biosynthetic defects in the fat body. In support of this conclusion, the protein content was much higher in larvae fed high Mg2+ on day 3 only, than in larvae maintained continuously on food with normal levels of Mg2+. These larvae, in contrast to larvae kept continuously on low Mg2+, displayed nearly normal hemolymph proteins. We propose that during early larval development when most larval growth is taking place, high Mg2+ in the diet is deleterious to trpm larvae because the hypermagnesemia suppresses feeding behavior and growth of tissues such as the fat bodies, which is a prerequisite for anabolic function. However, once morphogenesis and tissue growth is largely complete, as in late stage larvae, the high Mg2+ may contribute to Mg2+ resorption in tissues such as the fat bodies (Figure 6), thereby promoting biosynthetic function.

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