Acute regulation of Na+/H+ exchanger NHE3 by parathyroid hormone via NHE3 phosphorylation and dynamin-dependent endocytosis

被引:96
作者
Collazo, R
Fan, LZ
Hu, MC
Zhao, H
Wiederkehr, MR
Moe, OW
机构
[1] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA
[2] Vet Affairs Med Ctr, Med Serv, Dallas, TX 75235 USA
关键词
D O I
10.1074/jbc.M000600200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Parathyroid hormone (PTH) is a potent inhibitor of mammalian renal proximal tubule Na+ transport via its action on the apical membrane Na+/H+ exchanger NHE3. In the opossum kidney cell line, inhibition of NHE3 activity was detected from 5 to 45 min after PTH addition. Increase in NHE3 phosphorylation on multiple serines was evident after 5 min of PTH, but decrease in surface NHE3 antigen was not detectable until after 30 min of PTH. The decrease in surface NHE3 antigen was due to increased NHE3 endocytosis. When endocytic trafficking was arrested with a dominant negative dynamin mutant (K44A), the early inhibition (5 min) of NHE3 activity by PTH was not affected, whereas the late inhibition (30 min) and decreased surface NHE3 antigen induced by PTH were abrogated. We conclude that PTH acutely inhibits NHE3 activity in a biphasic fashion by NHE3 phosphorylation followed by dynamin-dependent endocytosis.
引用
收藏
页码:31601 / 31608
页数:8
相关论文
共 86 条
[1]   EFFECTS OF PARATHYROID-HORMONE ON RENAL TUBULAR REABSORPTION OF CALCIUM, SODIUM, AND PHOSPHATE [J].
AGUS, ZS ;
GARDNER, LB ;
BECK, LH ;
GOLDBERG, M .
AMERICAN JOURNAL OF PHYSIOLOGY, 1973, 224 (05) :1143-1148
[2]   Redundant and distinct functions for dynamin-1 and dynamin-2 isoforms [J].
Altschuler, Y ;
Barbas, SM ;
Terlecky, LJ ;
Tang, K ;
Hardy, S ;
Mostov, KE ;
Schmid, SL .
JOURNAL OF CELL BIOLOGY, 1998, 143 (07) :1871-1881
[3]   EXPRESSION OF NHE-3 IN THE APICAL MEMBRANE OF RAT RENAL PROXIMAL TUBULE AND THICK ASCENDING LIMB [J].
AMEMIYA, M ;
LOFFING, J ;
LOTSCHER, M ;
KAISSLING, B ;
ALPERN, RJ ;
MOE, OW .
KIDNEY INTERNATIONAL, 1995, 48 (04) :1206-1215
[4]   Structurally diverse N-terminal peptides of parathyroid hormone (PTH) and PTH-related peptide (PTHRP) inhibit the Na+/H+ exchanger NHE3 isoform by binding to the PTH/PTHRP receptor type I and activating distinct signaling pathways [J].
Azarani, A ;
Goltzman, D ;
Orlowski, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (25) :14931-14936
[5]   PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PEPTIDE INHIBIT THE APICAL NA+/H+ EXCHANGER NHE-3 ISOFORM IN RENAL-CELLS (OK) VIA A DUAL SIGNALING CASCADE INVOLVING PROTEIN-KINASE-A AND PROTEIN-KINASE-C [J].
AZARANI, A ;
GOLTZMAN, D ;
ORLOWSKI, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (34) :20004-20010
[6]   MICROPUNCTURE STUDY OF EFFECT OF PARATHYROID-HORMONE ON RENAL BICARBONATE REABSORPTION [J].
BANK, N ;
AYNEDJIAN, HS .
JOURNAL OF CLINICAL INVESTIGATION, 1976, 58 (02) :336-344
[7]  
BERTRAND B, 1994, J BIOL CHEM, V269, P13703
[8]   NHE3 - A NA+/H+ EXCHANGER ISOFORM OF RENAL BRUSH-BORDER [J].
BIEMESDERFER, D ;
PIZZONIA, J ;
ABUALFA, A ;
EXNER, M ;
REILLY, R ;
IGARASHI, P ;
ARONSON, PS .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 265 (05) :F736-F742
[9]   Monoclonal antibodies for high-resolution localization of NHE3 in adult and neonatal rat kidney [J].
Biemesderfer, D ;
Rutherford, PA ;
Nagy, T ;
Pizzonia, JH ;
AbuAlfa, AK ;
Aronson, PS .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1997, 273 (02) :F289-F299
[10]   Specific association of megalin and the Na+/H+ exchanger isoform NHE3 in the proximal tubule [J].
Biemesderfer, D ;
Nagy, T ;
DeGray, B ;
Aronson, PS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (25) :17518-17524