Journal article
A putative amino acid transporter of the solute carrier 6 family is upregulated by lithium and is required for resistance to lithium toxicity in Drosophila
Neuroscience, Vol.163(3), pp.825-837
2009
DOI: 10.1016/j.neuroscience.2009.07.027
PMID: 19619614
Abstract
Lithium is an efficacious drug for the treatment of mood disorders, and its application is also considered a potential therapy for brain damage. However, the mechanisms underlying lithium's therapeutic action and toxic effects in the nervous system remain largely elusive. Here we report on the use of a versatile genetic model, the fruit fly
Drosophila melanogaster, to discover novel molecular components involved in the lithium-responsive neurobiological process. We previously identified
CG15088, which encodes a putative nutrient amino acid transporter of the solute carrier 6 (SLC6) family, as one of the genes most significantly upregulated in response to lithium treatment. This gene was the only SLC6 gene induced by lithium, and was thus designated as
Lithium-inducible SLC6 transporter or
List. Either RNA interference (RNAi)–mediated knockdown or complete deletion of
List resulted in a remarkable increase in the susceptibility of adult flies to lithium's toxic effects, whereas transgenic expression of wild-type
List significantly suppressed the lithium hypersensitive phenotype of
List-deficient flies. Other ions such as sodium, potassium and chloride did not induce
List upregulation, nor did they affect the viability of flies with suppressed
List expression. These results indicate that lithium's biochemical or physical properties, rather than general osmotic responses, are responsible for the lithium-induced upregulation of
List, as well as for the lithium-susceptible phenotype observed in
List knockdown flies. Interestingly, flies became significantly more susceptible to lithium toxicity when
List RNAi was specifically expressed in glia than when it was expressed in neurons or muscles, which is consistent with potential glial expression of
List. These results show that the
List transporter confers resistance to lithium toxicity, possibly as a consequence of its amino acid transporter activity in CNS glia. Our results have provided a new avenue of investigation toward a better understanding of the molecular and cellular mechanisms that underlie lithium-responsive neurobiological process.
Details
- Title: Subtitle
- A putative amino acid transporter of the solute carrier 6 family is upregulated by lithium and is required for resistance to lithium toxicity in Drosophila
- Creators
- J Kasuya - Department of Anesthesia, Carver College of Medicine, University of Iowa, 1-316 BSB, 51 Newton Road, Iowa City, IA 52242, USAG.A Kaas - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA 52242, USAT Kitamoto - Department of Anesthesia, Carver College of Medicine, University of Iowa, 1-316 BSB, 51 Newton Road, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.163(3), pp.825-837
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.neuroscience.2009.07.027
- PMID
- 19619614
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Language
- English
- Date published
- 2009
- Academic Unit
- Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984006355702771
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