Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers

被引:151
作者
Pang, TX [1 ]
Su, XH [1 ]
Wakabayashi, S [1 ]
Shigekawa, R [1 ]
机构
[1] Natl Cardiovasc Ctr, Res Inst, Dept Mol Physiol, Suita, Osaka 5658565, Japan
关键词
D O I
10.1074/jbc.M100296200
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
The Na+/H+ exchangers (NHEs) comprise a family of transporters that catalyze cell functions such as regulation of the pH and volume of a cell and epithelial absorption of Na+ and bicarbonate. Ubiquitous calcineurin B homologous protein (CHP or p22) is co-localized and co-immunoprecipitated with expressed NHE1, NHE2, or NHE3 independently of its myristoylation and Ca2+ binding, and its binding site was identified as the jux-tamembrane region within the carboxyl-terminal cytoplasmic domain of exchangers. CHP binding-defective mutations of NHE1-3 or CHP depletion by injection of the competitive CHP-binding region of NHE1 into Xeno-pus oocytes resulted in a dramatic reduction (> 90%) in the Na+/H+ exchange activity. The data suggest that CHP serves as an essential cofactor, which supports the physiological activity of NHE family members.
引用
收藏
页码:17367 / 17372
页数:6
相关论文
共 26 条
  • [1] Intracellular pH regulation by Na+/H+ exchange requires phosphatidylinositol 4,5-bisphosphate
    Aharonovitz, O
    Zaun, HC
    Balla, T
    York, JD
    Orlowski, J
    Grinstein, S
    [J]. JOURNAL OF CELL BIOLOGY, 2000, 150 (01) : 213 - 224
  • [2] Molecular cloning, genomic organization, and functional expression of Na+/H+ exchanger isoform 5 (NHE5) from human brain
    Baird, NR
    Orlowski, J
    Szabó, EZ
    Zaun, HC
    Schultheis, PJ
    Menon, AG
    Shull, GE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (07) : 4377 - 4382
  • [3] A novel Ca2+-binding protein, p22, is required for constitutive membrane traffic
    Barroso, MR
    Bernd, KK
    DeWitt, ND
    Chang, A
    Mills, K
    Sztul, ES
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (17) : 10183 - 10187
  • [4] BERTRAND B, 1994, J BIOL CHEM, V269, P13703
  • [5] Cloning and sequencing of the cDNA encoding for a Na+/H+ exchanger from Xenopus laevis oocytes (X1-NHE)
    Busch, S
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1997, 1325 (01): : 13 - 16
  • [6] THE NA+/H+ EXCHANGER NHE-1 POSSESSES N-LINKED AND O-LINKED GLYCOSYLATION RESTRICTED TO THE FIRST N-TERMINAL EXTRACELLULAR DOMAIN
    COUNILLON, L
    POUYSSEGUR, J
    REITHMEIER, RAF
    [J]. BIOCHEMISTRY, 1994, 33 (34) : 10463 - 10469
  • [7] Sodium/hydrogen exchanger gene defect in slow-wave epilepsy mutant mice
    Cox, GA
    Lutz, CM
    Yang, CL
    Biemesderfer, D
    Bronson, RT
    Fu, A
    Aronson, PS
    Noebels, JL
    Frankel, WN
    [J]. CELL, 1997, 91 (01) : 139 - 148
  • [8] Ikeda T, 1997, J BIOCHEM-TOKYO, V121, P295
  • [9] CRYSTAL-STRUCTURES OF HUMAN CALCINEURIN AND THE HUMAN FKBP12-FK506-CALCINEURIN COMPLEX
    KISSINGER, CR
    PARGE, HE
    KNIGHTON, DR
    LEWIS, CT
    PELLETIER, LA
    TEMPCZYK, A
    KALISH, VJ
    TUCKER, KD
    SHOWALTER, RE
    MOOMAW, EW
    GASTINEL, LN
    HABUKA, N
    CHEN, XH
    MALDONADO, F
    BARKER, JE
    BACQUET, R
    VILLAFRANCA, JE
    [J]. NATURE, 1995, 378 (6557) : 641 - 644
  • [10] A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange
    Lin, X
    Barber, DL
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (22) : 12631 - 12636