Expression and regulation of the renal Na/phosphate cotransporter NaPi-IIa in a mouse model deficient for the PDZ protein PDZK1

被引:51
作者
Capuano, P
Bacic, D
Stange, G
Hernando, N
Kaissling, B
Pal, R
Kocher, O
Biber, J
Wagner, CA
Murer, H
机构
[1] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland
[2] Univ Zurich, Inst Anat, Zurich, Switzerland
[3] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA
[4] Harvard Univ, Sch Med, Boston, MA 02115 USA
来源
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY | 2005年 / 449卷 / 04期
关键词
PDZ proteins; proximal tubule; phosphate transport; brush border membrane; NHERF; PDZK1; mouse;
D O I
10.1007/s00424-004-1351-9
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Inorganic phosphate (Pi) is reabsorbed in the renal proximal tubule mainly via the type-IIa sodium-phosphate cotransporter (NaPi-IIa). This protein is regulated tightly by different factors, among them dietary Pi intake and parathyroid hormone (PTH). A number of PDZ-domain-containing proteins have been shown to interact with NaPi-IIa in vitro, such as Na+/H+ exchanger-3 regulatory factor-1 (NHERF1) and PDZK1. PDZK1 is highly abundant in kidney and co-localizes with NaPi-IIa in the brush border membrane of proximal tubules. Recently, a knock-out mouse model for PDZK1 (Pdzk1(-/-)) has been generated, allowing the role of PDZK1 in the expression and regulation of the NaPi-IIa cotransporter to be examined in in vivo and in ex vivo preparations. The localization of NaPi-IIa and other proteins interacting with PDZK1 in vitro [Na+/H+ exchanger (NHE3), chloride-formate exchanger (CFEX)/putative anion transporter-1 (PAT1), NHERF1] was not altered in Pdzkl(-/-) mice. The abundance of NaPi-IIa adapted to acute and chronic changes in dietary Pi intake, but steady-state levels of NaPi-IIa were reduced in Pdzk1(-/-) under a Pi rich diet. This was paralleled I by a higher urinary fractional Pi excretion. The abundance of the anion exchanger CFEX/PAT1 (SLC26A6) was also reduced. In contrast, NHERF1 abundance increased in the brush border membrane of Pdzk1(-/-) mice fed a high-Pi diet. Acute regulation of NaPi-IIa by PTH in vivo and by PTH and activators of protein kinases A, C and G (PKA, PKC and PKG) in vitro (kidney slice preparation) was not altered in Pdzk1(-/-) mice. In conclusion, loss of PDZK1 did not result in major changes in proximal tubule function or NaPi-IIa regulation. However, under a Pi-rich diet, loss of PDZK1 reduced NaPi-IIa abundance indicating that PDZK1 may play a role in the trafficking or stability of NaPi-IIa under these conditions.
引用
收藏
页码:392 / 402
页数:11
相关论文
共 28 条
  • [1] Impaired PTH-induced endocytotic down-regulation of the renal type IIa Na+/Pi-cotransporter in RAP-deficient mice with reduced megalin expression
    Bacic, D
    Capuano, P
    Gisler, SM
    Pribanic, S
    Christensen, EI
    Biber, J
    Loffing, J
    Kaissling, B
    Wagner, CA
    Murer, H
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2003, 446 (04): : 475 - 484
  • [2] Involvement of the MAPK-kinase pathway in the PTH-mediated regulation of the proximal tubule type IIa Na+/Pi cotransporter in mouse kidney
    Bacic, D
    Schulz, N
    Biber, J
    Kaissling, B
    Murer, H
    Wagner, CA
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2003, 446 (01): : 52 - 60
  • [3] Regulation of the renal type IIa Na/Pi cotransporter by cGMP
    Bacic, D
    Hernando, N
    Traebert, M
    Lederer, E
    Völkl, H
    Biber, J
    Kaissling, B
    Murer, H
    [J]. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2001, 443 (02): : 306 - 313
  • [4] A HIGH-YIELD PREPARATION FOR RAT-KIDNEY BRUSH-BORDER MEMBRANES - DIFFERENT BEHAVIOR OF LYSOSOMAL MARKERS
    BIBER, J
    STIEGER, B
    HAASE, W
    MURER, H
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1981, 647 (02) : 169 - 176
  • [5] Defective parathyroid hormone regulation of NHE3 activity and phosphate adaptation in cultured NHERF-1-/- renal proximal tubule cells
    Cunninghan, R
    Steplock, D
    Wang, FY
    Huang, HJ
    E, XF
    Shenolikar, S
    Weinman, EJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (36) : 37815 - 37821
  • [6] EXPRESSION OF NA-P-I COTRANSPORT IN RAT-KIDNEY - LOCALIZATION BY RT-PCR AND IMMUNOHISTOCHEMISTRY
    CUSTER, M
    LOTSCHER, M
    BIBER, J
    MURER, H
    KAISSLING, B
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (05): : F767 - F774
  • [7] ECTO-5'-NUCLEOTIDASE - LOCALIZATION IN RAT-KIDNEY BY LIGHT MICROSCOPIC HISTOCHEMICAL AND IMMUNOHISTOCHEMICAL METHODS
    DAWSON, TP
    GANDHI, R
    LEHIR, M
    KAISSLING, B
    [J]. JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1989, 37 (01) : 39 - 47
  • [8] PDZK1: II. An anchoring site for the PKA-binding protein D-AKAP2 in renal proximal tubular cells
    Gisler, SM
    Madjdpour, C
    Bacic, D
    Pribanic, S
    Taylor, SS
    Biber, J
    Murer, H
    [J]. KIDNEY INTERNATIONAL, 2003, 64 (05) : 1746 - 1754
  • [9] PDZK1: I. A major scaffolder in brush borders of proximal tubular cells
    Gisler, SM
    Pribanic, S
    Bacic, D
    Forrer, P
    Gantenbein, A
    Sabourin, LA
    Tsuji, A
    Zhao, ZS
    Manser, E
    Biber, J
    Murer, H
    [J]. KIDNEY INTERNATIONAL, 2003, 64 (05) : 1733 - 1745
  • [10] Interaction of the type IIa Na/Pi cotransporter with PDZ proteins
    Gisler, SM
    Stagljar, I
    Traebert, M
    Bacic, D
    Biber, J
    Murer, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (12) : 9206 - 9213