Down-regulation of volume-sensitive Cl- channels by CFTR is mediated by the second nucleotide-binding domain

被引:31
作者
Ando-Akatsuka, Y
Abdullaev, IF
Lee, EL
Okada, Y
Sabirov, RZ [1 ]
机构
[1] Natl Inst Physiol Sci, Dept Cell Physiol, Okazaki, Aichi 4448585, Japan
[2] JST, CREST, Okazaki, Aichi 4448585, Japan
[3] Grad Univ Adv Studies, Sch Life Sci, Dept Physiol Sci, Okazaki, Aichi 4448585, Japan
来源
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY | 2002年 / 445卷 / 02期
关键词
CFTR; chloride channels; mutagenesis; NBD2; osmotic cell swelling; VSOR;
D O I
10.1007/s00424-002-0920-z
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Transient expression of wild-type human cystic fibrosis transmembrane conductance regulator (CFTR) in HEK293T cells resulted in a profound decrease in the amplitude of volume-sensitive outwardly rectifying Cl- channel (VSOR) current without changing the single-channel amplitude. This effect was not mimicked by expression of the DeltaF508 mutant of CFTR, which did not reach the plasma membrane. The VSOR regulation by CFTR was not affected by G551D mutation at first nucleotide-binding domain (NBD1), which is known to impair CFTR interaction with the outwardly rectifying chloride channel, ORCC, epithelial amiloride-sensitive Na-channel, ENaC, and renal potassium channel, ROMK2. The CFTR-VSOR interaction was insensitive to the deletion mutation, DeltaTRL, which is known to impair CFTR-PDZ domain binding. In contrast, the G1349D mutant, which impairs ATP binding at NBD2, effectively abolished the down-regulatory effect of CFTR. Furthermore, the K1250M mutation at the Walker A motif and the D1370N mutation at the Walker B motif, both known to impair ATP hydrolysis at NBD2, completely abolished the VSOR regulation by CFTR. Thus, we conclude that an ATP-hydrolysable conformation of NBD2 is essential for the regulation of the VSOR by the CFTR protein, and that VSOR is a first channel regulated by CFTR through its NBD2.
引用
收藏
页码:177 / 186
页数:10
相关论文
共 58 条
[11]   CONFORMATIONAL STATES OF CFTR ASSOCIATED WITH CHANNEL GATING - THE ROLE OF ATP BINDING AND HYDROLYSIS [J].
GUNDERSON, KL ;
KOPITO, RR .
CELL, 1995, 82 (02) :231-239
[12]   Cystic fibrosis transmembrane conductance regulator and the outwardly rectifying chloride channel: A relationship between two chloride channels expressed in epithelial cells [J].
Hryciw, DH ;
Guggino, WB .
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2000, 27 (11) :892-895
[13]   PDZ domains: Structural modules for protein complex assembly [J].
Hung, AY ;
Sheng, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (08) :5699-5702
[14]   Cystic fibrosis transmembrane conductance regulator mediates sulphonylurea block of the inwardly rectifying K+ channel Kir6.1 [J].
Ishida-Takahashi, A ;
Otani, H ;
Takahashi, C ;
Washizuka, T ;
Tsuji, K ;
Noda, M ;
Horie, M ;
Sasayama, S .
JOURNAL OF PHYSIOLOGY-LONDON, 1998, 508 (01) :23-30
[15]  
Ismailov II, 1996, J BIOL CHEM, V271, P4725
[16]   CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR IS REQUIRED FOR PROTEIN-KINASE-A ACTIVATION OF AN OUTWARDLY RECTIFIED ANION CHANNEL PURIFIED FROM BOVINE TRACHEAL EPITHELIA [J].
JOVOV, B ;
ISMAILOV, II ;
BENOS, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (04) :1521-1528
[17]   INTERACTION BETWEEN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR AND OUTWARDLY RECTIFIED CHLORIDE CHANNELS [J].
JOVOV, B ;
ISMAILOV, II ;
BERDIEV, BK ;
FULLER, CM ;
SORSCHER, EJ ;
DEDMAN, JR ;
KAETZEL, MA ;
BENOS, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (49) :29194-29200
[18]   VOLUME-REGULATORY CL- CHANNEL CURRENTS IN CULTURED HUMAN EPITHELIAL-CELLS [J].
KUBO, M ;
OKADA, Y .
JOURNAL OF PHYSIOLOGY-LONDON, 1992, 456 :351-371
[19]   The cystic fibrosis transmembrane conductance regulator attenuates the endogenous Ca2+ activated Cl- conductance of Xenopus oocytes [J].
Kunzelmann, E ;
Mall, M ;
Briel, M ;
Hipper, A ;
Nitschke, R ;
Ricken, S ;
Greger, R .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1997, 435 (01) :178-181
[20]   CFTR, a regulator of channels [J].
Kunzelmann, K ;
Schreiber, R .
JOURNAL OF MEMBRANE BIOLOGY, 1999, 168 (01) :1-8