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Open Access Research article

Evaluation of expression and function of the H+/myo-inositol transporter HMIT

Elena Di Daniel1*, Man HS Mok1, Emma Mead1, Chiara Mutinelli2, Erika Zambello2, Laura L Caberlotto2, Theresa J Pell1, Christopher J Langmead1, Ajit J Shah4, Graham Duddy3, James NC Kew1 and Peter R Maycox1

Author Affiliations

1 Psychiatry Discovery Technology Group, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK

2 Psychiatry Discovery Technology Group, GlaxoSmithKline, New Frontiers Science Park, Verona, Italy

3 Core Discovery Technology Group, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK

4 Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK

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BMC Cell Biology 2009, 10:54  doi:10.1186/1471-2121-10-54

Published: 16 July 2009

Abstract

Background

The phosphoinositide (PIns) signalling pathway regulates a series of neuronal processes, such as neurotransmitter release, that are thought to be altered in mood disorders. Furthermore, mood-stabilising drugs have been shown to inhibit key enzymes that regulate PIns production and alter neuronal growth cone morphology in an inositol-reversible manner. Here, we describe analyses of expression and function of the recently identified H+/myo-inositol transporter (HMIT) investigated as a potential regulator of PIns signalling.

Results

We show that HMIT is primarily a neuronal transporter widely expressed in the rat and human brain, with particularly high levels in the hippocampus and cortex, as shown by immunohistochemistry. The transporter is localised at the Golgi apparatus in primary cultured neurones. No HMIT-mediated electrophysiological responses were detected in rat brain neurones or slices; in addition, inositol transport and homeostasis were unaffected in HMIT targeted null-mutant mice.

Conclusion

Together, these data do not support a role for HMIT as a neuronal plasma membrane inositol transporter, as previously proposed. However, we observed that HMIT can transport inositol triphosphate, indicating unanticipated intracellular functions for this transporter that may be relevant to mood control.