Molecular cloning of a novel brain-type Na+-dependent inorganic phosphate cotransporter

We have isolated a human cDNA encoding a protein, designated DNPI, that sho ws 82% amino acid identity and 92% similarity to the human brain-specific N a+-dependent inorganic phosphate (Na+/P-i) cotransporter (BNPI), which is l ocalized exclusively to neuron-rich regions. Expression of DNPI mRNA in Xen opus oocytes resulted in a significant increase in Na+-dependent P-i transp ort, indicating that DNPI is a novel Na+/P-i cotransporter. Northern blot a nalysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucl eus, and thalamus, all of which express BNPI mRNA at low levels. In contras t, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, wher e BNPI mRNA is expressed at high levels. No hybridizing signal for DNPI mRN A is observed in the glia-rich region of corpus callosum. In other regions examined, both mRNAs are moderately or highly expressed. These results indi cate that BNPI and DNPI, which coordinate Na+-dependent P-i transport in th e neuron-rich regions of the brain, may form a new class within the Na+/P-i cotransporter family.