A slow pH-dependent conformational transition underlies a novel mode of activation of the epithelial Na+/H+ exchanger-3 isoform

被引:29
作者
Hayashi, H
Szászi, K
Coady-Osberg, N
Orlowski, J
Kinsella, JL
Grinstein, S
机构
[1] Hosp Sick Children, Res Inst, Cell Biol Program, Toronto, ON M5G 1X8, Canada
[2] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada
[3] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA
关键词
D O I
10.1074/jbc.M111868200
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
Allosteric control of Na+/H- exchange by intracellular protons ensures rapid and accurate regulation of the intracellular pH. Although this allosteric effect was heretofore thought to occur almost instantaneously, we report here the occurrence of a slower secondary activation of the epithelial Na+/H- exchanger (NHE)-3 isoform. This slow activation mode developed over the course of minutes and was unique to NHE3 and the closely related isoform NHE5, but was not observed in NHE1 or NHE2. Activation of NHE3 was not due to increased density of exchangers at the cell surface, nor was it accompanied by detectable changes in phosphorylation. The association of NHE3 with the cytoskeleton, assessed by its retention in the detergent-insoluble fraction, was similarly unaffected by acidification. In contrast to the slow progressive activation elicited by acidification, deactivation occurred very rapidly upon restoration of the physiological pH. We propose that NHE3 undergoes a slow pH-dependent transition from a less active to a more active state, likely by changing its conformation or state of association.
引用
收藏
页码:11090 / 11096
页数:7
相关论文
共 38 条
[1]   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
[2]   MODIFIER ROLE OF INTERNAL H+ IN ACTIVATING THE NA+-H+ EXCHANGER IN RENAL MICROVILLUS MEMBRANE-VESICLES [J].
ARONSON, PS ;
NEE, J ;
SUHM, MA .
NATURE, 1982, 299 (5879) :161-163
[3]   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
[4]   SODIUM-DEPENDENT PHOSPHATE-TRANSPORT BY APICAL MEMBRANE-VESICLES FROM A CULTURED RENAL EPITHELIAL-CELL LINE (LLC-PK1) [J].
BROWN, CDA ;
BODMER, M ;
BIBER, J ;
MURER, H .
BIOCHIMICA ET BIOPHYSICA ACTA, 1984, 769 (02) :471-478
[5]   The expanding family of eucaryotic Na+/H+ exchangers [J].
Counillon, L ;
Pouysségur, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (01) :1-4
[6]   The epithelial sodium-hydrogen antiporter Na+/H+ exchanger 3 accumulates and is functional in recycling endosomes [J].
D'Souza, S ;
Garcia-Cabado, A ;
Yu, F ;
Teter, K ;
Lukacs, G ;
Skorecki, K ;
Moore, HP ;
Orlowski, J ;
Grinstein, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (04) :2035-2043
[7]   FUNCTIONAL EXPRESSION OF A HUMAN NA+/H+ ANTIPORTER GENE TRANSFECTED INTO ANTIPORTER-DEFICIENT MOUSE L CELLS [J].
FRANCHI, A ;
PERUCCALOSTANLEN, D ;
POUYSSEGUR, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (24) :9388-9392
[8]   USE OF A SCANNING DENSITOMETER OR AN ELISA PLATE READER FOR MEASUREMENT OF NANOGRAM AMOUNTS OF PROTEIN IN CRUDE EXTRACTS FROM BIOLOGICAL TISSUES [J].
GHOSH, S ;
GEPSTEIN, S ;
HEIKKILA, JJ ;
DUMBROFF, EB .
ANALYTICAL BIOCHEMISTRY, 1988, 169 (02) :227-233
[9]   CYTOPLASMIC PH REGULATION IN THYMIC LYMPHOCYTES BY AN AMILORIDE-SENSITIVE NA+/H+ ANTIPORT [J].
GRINSTEIN, S ;
COHEN, S ;
ROTHSTEIN, A .
JOURNAL OF GENERAL PHYSIOLOGY, 1984, 83 (03) :341-369
[10]   NA-22+ FLUXES IN THYMIC LYMPHOCYTES .2. AMILORIDE-SENSITIVE NA+/H+ EXCHANGE PATHWAY - REVERSIBILITY OF TRANSPORT AND ASYMMETRY OF THE MODIFIER SITE [J].
GRINSTEIN, S ;
GOETZ, JD ;
ROTHSTEIN, A .
JOURNAL OF GENERAL PHYSIOLOGY, 1984, 84 (04) :585-600