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.
Uldry
M
M
Institute of Pharmacology and Toxicology, University of Lausanne, Lausanne, Switzerland.
Ibberson
M
M
Horisberger
J D
JD
Chatton
J Y
JY
Riederer
B M
BM
Thorens
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D002461:Cell Line, Transformed; D018076:DNA, Complementary; D004594:Electrophysiology; D051246:Glucose Transport Proteins, Facilitative; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007294:Inositol / Q000378:metabolism*; D007424:Intracellular Fluid; D008322:Mammals; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger; D051381:Rats; D014981:Xenopus
D018076:DNA, Complementary; D051246:Glucose Transport Proteins, Facilitative; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C437315:SLC2A13 protein, human; C486673:Slc2a13 protein, rat; D007294:Inositol