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


CONCLUSIONS
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.
Di Daniel
Elena
E
Psychiatry Discovery Technology Group, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK. Elena.2.DiDaniel@gsk.com
Mok
Man H S
MH
Mead
Emma
E
Mutinelli
Chiara
C
Zambello
Erika
E
Caberlotto
Laura L
LL
Pell
Theresa J
TJ
Langmead
Christopher J
CJ
Shah
Ajit J
AJ
Duddy
Graham
G
Kew
James N C
JN
Maycox
Peter R
PR
D000818:Animals; D001921:Brain / Q000166:cytology*; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017353:Gene Deletion; D051246:Glucose Transport Proteins, Facilitative / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D051246:Glucose Transport Proteins, Facilitative; C437315:SLC2A13 protein, human; C544447:SLC2A13 protein, mouse; C486673:Slc2a13 protein, rat; D007294:Inositol