The type III transporters (PiT-1 and PiT-2) are the major sodium-dependent phosphate transporters in the mice and human brains

Abstract

PiT-1/SLC20A1 and PiT-2/SLC20A2 are members of the mammalian type-III inorganic phosphate (Pi) transporters encoded by the SLC20 genes. The broad distribution of SLC20A1 and SLC20A2 mRNAs in mammalian tissues is compatible with housekeeping maintenance of intracellular Pi homeostasis by transporting Pi from intrastitial fluid for normal cellular functions. Recently, mutations of SLC20A2 have been found in patients with idiopathic basal ganglia calcification (IBGC), also known as Fahr's disease. However, the localization of PiT-1 and PiT-2 in the normal brain has not been clarified yet. The aim of this study was to reveal the distribution of PiT-1 and PiT-2 in the mouse and human brains. As results, gene expressing analysis showed that SLC20A1 and SLC20A2 mRNAs were widely expressed throughout the mouse and human brains, although other Pi transporters encoded by SLC17 and SLC34 mRNAs were hardly detected. The region of cerebellum contained a higher level of SLC20A1 and SLC20A2 mRNAs than the other brain regions. Additionally, the cerebellum in the mouse brain contained higher levels of PiT-1 and PiT-2 than those in the other regions in the brain, respectively. The immunohistochemical studies showed that PiT-1 was recognized in neuron, astrocytes and vascular endothelial cells. Similarly to PiT-1 immunopositivity, PiT-2 was clearly recognized in these cells. These results suggest that SLC20 family plays a pivotal role in the maintenance of cellular Pi homeostasis particularly in the brain. The viewpoint is compatible with the finding that calcification in IBGC is recognized only in the brain. This provides us with a novel viewpoint to understand the basic pathophysiology of IBGC through type-III Pi transporters.

Keywords: Idiopathic basal ganglia calcification; Phosphate homeostasis; Phosphate transporter; PiT-1; PiT-2.