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Identification of a mammalian H(+)-myo-inositol symporter expressed predominantly in the brain.
Inositol and its phosphorylated derivatives play a major role in brain function, either as osmolytes, second messengers or regulators of vesicle endo- and exocytosis. Here we describe the identification and functional characterization of a novel H(+)-myo- inositol co-transporter, HMIT, expressed predominantly in the brain. HMIT cDNA encodes a 618 amino acid polypeptide with 12 predicted transmembrane domains. Functional expression of HMIT in Xenopus oocytes showed that transport activity was specific for myo-inositol and related stereoisomers with a Michaelis-Menten constant of approximately 100 microM, and that transport activity was strongly stimulated by decreasing pH. Electrophysiological measurements revealed that transport was electrogenic with a maximal transport activity reached at pH 5.0. In rat brain membrane preparations, HMIT appeared as a 75-90 kDa protein that could be converted to a 67 kDa band upon enzymatic deglycosylation. Immunofluorescence microscopy analysis showed HMIT expression in glial cells and some neurons. These data provide the first characterization of a mammalian H(+)-coupled myo- inositol transporter. Predominant central expression of HMIT suggests that it has a key role in the control of myo-inositol brain metabolism.
Amino Acid Sequence, Animals, Base Sequence, Brain, Cell Line, Transformed, DNA, Complementary, Electrophysiology, Glucose Transport Proteins, Facilitative, Humans, Hydrogen-Ion Concentration, Inositol, Intracellular Fluid, Mammals, Membrane Proteins, Microscopy, Fluorescence, Molecular Sequence Data, Monosaccharide Transport Proteins, RNA, Messenger, Rats, Xenopus
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