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+-myoinositol 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 inyo-inositol and related stereoisomers with a Michaelis-Menten constant of similar to 100 muM, 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 myoinositol transporter. Predominant central expression of HMIT suggests that it has a key role in the control of inyo-inositol brain metabolism.