Cell and Development Biology
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Eric Lambie

Cell Biology, Developmental Genetics, Magnesium Homeostasis

transgenetic-animal-lambieAll cells require magnesium in order to grow and divide. We use the nematode C. elegans as a model animal system to identify and characterize genes that are required for the proper uptake, utilization and excretion of magnesium. We are currently using a combination of genetic, molecular and cell biological approaches to investigate the function and regulation of evolutionarily conserved ion channels and transporters that we have identified as important for magnesium homeostasis during C. elegans development.

We have assessed the functions of three TRPM-like cation channels, GON-2, GTL-1 and GTL-2. GTL-1 is exclusively expressed in the intestine, where it mediates the uptake of Mg2+ from the gut lumen. GON-2 is also expressed in the intestine, where it functions in parallel to GTL-1. In addition, GON-2 is required within the gonadal precursor cells for the onset of gonadal cell divisions. GTL-2 is expressed within the excretory cell, where it mediates uptake of Mg2+ from the pseudocoelomic fluid.
Expression pattern of a GTL-2::GFP fusion
protein in a transgenic animal.

We have used a temperature sensitive mutation in gon-2 to screen for suppressor mutations that identify additional genes involved in Mg2+ homeostasis. One of the genes that we identified in these screens is gem-1 (gon-2 extragenic modifier). The predicted GEM-1 protein has similarity to mammalian monocarboxylate transporters, which have not been previously implicated in Mg2+ homeostasis.

gonad-lambie
Left panel is a DIC image of a live first stage larval animal. The somatic gonad precursor cell, Z1 (arrow), and the germline precursor cell, Z2 (arrowead), are indicated. Right panel is same animal, but imaged for GFP fluorescence. GEM-1::GFP localizes to the plasma membrane of Z1.

figure-lambie


The suppressor alleles of gem-1 (indicated above; with plasma membrane indicated by gray section) are distributed throughout the coding sequence; however, our genetic analyses indicate that each of these mutations somehow causes an elevation of GEM-1 activity. We are currently investigating the mechanism of action of the suppressor alleles of gem-1 and working to determine how hyperactivation of GEM-1 can compensate for the absence of GON-2 activity.