Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney.
We have demonstrated previously that the type-IIc Na/Pi cotransporter is a growth-related renal Na/Pi cotransporter that is highly expressed in kidney of the weaning rat. In the present study, we investigated type-IIc Na/Pi cotransporter function further by cloning the mouse gene and characterizing the corresponding protein. The mouse type-IIc transporter amino acid sequence shows a high degree of similarity to the human (86%) and rat (95%) type-IIc Na/Pi-cotransporters. The mouse gene contained 14 exons and mapped to chromosome 2. The DNA sequence upstream from exon 1 is GC rich. The upstream region does not contain an apparent TATA box, but does contain two dietary Pi-responsive elements, which are potential binding sites for the transcription factor micro E3 (TFE3). Microinjection of mouse type-IIc cRNA into Xenopus oocytes demonstrated sodium-dependent Pi cotransport activity. The affinity for Pi was about 200 microM in 100 mM Na. Feeding adult mice fed a low-Pi diet increased the expression of type-IIc protein in the apical membrane of renal proximal tubular cells. Hybrid depletion studies suggested that the type-IIc transporter contributes to about 30% of Na/Pi cotransport in the kidney of adult mice fed a low-Pi diet. The present study suggests that the type-IIc Na/Pi cotransporter is a functional of renal Pi transporter in adult mice fed a low-Pi diet.
Ohkido
I
I
Department of Nutrition, School of Medicine, Tokushima University, Kuramoto-cho 3, 770-850, Tokushima City, Japan.
Segawa
H
H
Yanagida
R
R
Nakamura
M
M
Miyamoto
K
K
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008871:Microvilli / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D009893:Opossums; D016226:Phosphorus, Dietary / Q000008:administration & dosage; D010957:Plasmids; D018075:RNA, Complementary / Q000378:metabolism; D051381:Rats; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution; D014162:Transfection; D014981:Xenopus
D016226:Phosphorus, Dietary; D018075:RNA, Complementary; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters