Interaction of a farnesylated protein with renal type IIa Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate.
Treatment with PTH (parathyroid hormone) or a high-P(i) diet causes internalization of the type IIa sodium-dependent phosphate (Na/P(i) IIa) co-transporter from the apical membrane and its degradation in the lysosome. A dibasic amino acid motif (KR) in the third intracellular loop of the co-transporter is essential for protein's PTH-induced retrieval. To elucidate the mechanism of internalization of Na/P(i) IIa, we identified the interacting protein for the endocytic motif by yeast two-hybrid screening. We found a strong interaction of the Na/P(i) IIa co-transporter with a small protein known as the PEX19 (human peroxisomal farnesylated protein; PxF, Pex19p). PEX19 can bind to the KR motif, but not to a mutant with this motif replaced with NI residues. PEX19 is highly expressed in mouse and rat kidney. Western blot analysis indicates that PEX19 is located in the cytosolic and brush-border membrane fractions (microvilli and the subapical component). Overexpression of PEX19 stimulated the endocytosis of the Na/P(i) IIa co-transporter in opossum kidney cells in the absence of PTH. In conclusion, the present study indicates that PEX19 may be actively involved in controlling the internalization and trafficking of the Na/P(i) IIa co-transporter.
Ito
Mikiko
M
Department of Nutrition, Tokushima University, School of Medicine, Kuramoto-cho 3-18-15, Tokushima City 770-8503, Japan.
Iidawa
Sachi
S
Izuka
Michiyo
M
Haito
Sakiko
S
Segawa
Hiroko
H
Kuwahata
Masashi
M
Ohkido
Ichiro
I
Ohno
Hiroshi
H
Miyamoto
Ken-Ichi
K
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000502:physiology; D015723:Gene Library; D006801:Humans; D007668:Kidney / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008871:Microvilli / Q000737:chemistry; D008969:Molecular Sequence Data; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry; D010710:Phosphates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D050608:Sodium-Phosphate Cotransporter Proteins; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D027981:Symporters / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D020798:Two-Hybrid System Techniques
D008565:Membrane Proteins; D010281:Parathyroid Hormone; D010455:Peptides; D010710:Phosphates; C493554:SLC34A1 protein, human; C493555:Slc34a1 protein, mouse; C493556:Slc34a1 protein, rat; D050608:Sodium-Phosphate Cotransporter Proteins; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D027981:Symporters; C087343:PEX19 protein, human; C018279:sodium phosphate