Identification of a mammalian H+-myo-inositol symporter expressed predominantly in the brain

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Abstract
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 ∼100 μM, 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.