Characterization and distribution of Hxt1, a Na+/Cl--dependent orphan transporter, in the human brain

Rxt1, a transporter-like protein structurally related to the large family o f Na+/Cl--dependent carriers, was isolated from the rat brain. In the prese nt study, Hxt1, the homologue of Rxt1, was isolated from human cortex cDNA, Comparison of their respective nucleotidic sequences revealed a 96% conser vation between Hxt1 and Rxt1, Genetic mapping with human genome radiation h ybrids allowed the location of the gene coding for Hxt1 between 323ya5 and 084xb3 AFM markers, on a portion of chromosome Ip which spans over 7 cM or 118 cRay. Northern blot analyses demonstrated that Hxt1 mRNA (similar to 7. 5 Kb) is expressed in the human brain but not in peripheral tissues. The im munodistribution of Hxt1 was determined with antibodies raised against the C-terminus of Rxt1, Hxt1 is concentrated in the cerebral cortex, caudate-pu tamen, substantia nigra, hippocampus, and cerebellum, appearing as a diffus e or a punctate labeling at the light microscope level, This regional and c ellular distribution suggests that Hxt1, as its rat homologue, could be pre sent in axon terminals of glutamatergic neurons, The high pressure of selec tion exerted upon this protein, its strategic anatomical and subcellular di stributions suggest that this orphan transporter could be involved in criti cal functions in the central nervous system. J. Neurosci, Res, 56:146-159, 1999, (C) 1999 Wiley-Liss, Inc.