Developmental NeuroscienceResearch PaperA putative amino acid transporter of the solute carrier 6 family is upregulated by lithium and is required for resistance to lithium toxicity in Drosophila
Section snippets
Fly stocks and culture conditions
Flies were reared at 25 °C in a 12-h light/dark cycle, on a conventional cornmeal/glucose/yeast/agar medium supplemented with the mold inhibitor methyl 4-hydroxybenzoate (0.05%). The Canton-S (CS) strain was used as the wild-type control. daughterless (da)-GAL4, Actin5C (Act5C)-GAL4, and tubulin (tub)-GAL4 were obtained from Wayne Johnson (University of Iowa, Iowa City, IA, USA). embryonic lethal abnormal vision (elav)-GAL4 on the X chromosome was obtained from Pam Geyer (University of Iowa,
An RNAi transgene effectively suppresses expression of the lithium-inducible SLC6 family transporter gene List
In our recent microarray-based gene expression analysis, CG15088 was identified as one of the genes in the Drosophila head that are most significantly upregulated by lithium treatment (Kasuya et al., 2009). CG15088 encodes a member of the SLC6 transporter family (Thimgan et al 2006, Romero-Calderon et al 2007). In the previous report (Miller et al., 2008), it was tentatively referred to as dmNAT2 for Drosophila melanogaster NAT2, based solely on its sequence similarity to the NAT1 gene, dmNAT1.
Discussion
Here we have shown that the suppression or complete deletion of List, the Drosophila lithium-inducible SLC6 gene that encodes a putative amino acid transporter, leads to a remarkable increase in the fly's susceptibility to lithium, and that glial expression of List is the primary requirement for resistance to lithium toxicity. Our results have identified the List transporter as a novel molecular player that is critically involved in mediating the physiological effects of lithium. In addition,
Acknowledgments
This study was supported by grants from the NIH (R03 MH078271), American Parkinson's Disease Association Research (APDA) and National Alliance for Research on Schizophrenia and Depression (NARSAD) to T.K.
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