Evolutionary origins of eukaryotic sodium/proton exchangers

被引:445
作者
Brett, CL
Donowitz, M
Rao, R
机构
[1] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2005年 / 288卷 / 02期
关键词
Na+/H+ exchanger; NHX; cation proton antiporter; phylogenetic analysis;
D O I
10.1152/ajpcell.00360.2004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
More than 200 genes annotated as Na+/H+ hydrogen exchangers (NHEs) currently reside in bioinformation databases such as GenBank and Pfam. We performed detailed phylogenetic analyses of these NHEs in an effort to better understand their specific functions and physiological roles. This analysis initially required examining the entire monovalent cation proton antiporter (CPA) superfamily that includes the CPA1, CPA2, and NaT-DC families of transporters, each of which has a unique set of bacterial ancestors. We have concluded that there are nine human NHE (or SLC9A) paralogs as well as two previously unknown human CPA2 genes, which we have named HsNHA1 and HsNHA2. The eukaryotic NHE family is composed of five phylogenetically distinct clades that differ in subcellular location, drug sensitivity, cation selectivity, and sequence length. The major subgroups are plasma membrane (recycling and resident) and intracellular (endosomal/TGN, NHE8-like, and plant vacuolar). HsNHE1, the first cloned eukaryotic NHE gene, belongs to the resident plasma membrane clade. The latter is the most recent to emerge, being found exclusively in vertebrates. In contrast, the intracellular clades are ubiquitously distributed and are likely precursors to the plasma membrane NHE. Yeast endosomal ScNHX1 was the first intracellular NHE to be described and is closely related to HsNHE6, HsNHE7, and HsNHE9 in humans. Our results link the appearance of NHE on the plasma membrane of animal cells to the use of the Na+/K+-ATPase to generate the membrane potential. These novel observations have allowed us to use comparative biology to predict physiological roles for the nine human NHE paralogs and to propose appropriate model organisms in which to study the unique properties of each NHE subclass.
引用
收藏
页码:C223 / C239
页数:17
相关论文
共 176 条
[1]   Characterization of Na+/H+ exchanger isoform (NHE1, NHE2 and NHE3) expression in prairie dog gallbladder [J].
Abedin, MZ ;
Giurgiu, DIN ;
Abedin, ZR ;
Peck, EA ;
Su, X ;
Smith, PR .
JOURNAL OF MEMBRANE BIOLOGY, 2001, 182 (02) :123-134
[2]   Inhibition of Na+/H+ exchanger type 3 reduces duration of apnea induced by laryngeal stimulation in piglets [J].
Abu-Shaweesh, JM ;
Dreshaj, IA ;
Martin, RJ ;
Wirth, KJ ;
Heinelt, U ;
Haxhiu, MA .
PEDIATRIC RESEARCH, 2002, 52 (03)
[3]  
Agalakova NI, 2003, COMP BIOCHEM PHYS A, V134, P13
[4]   Na+/H+ exchanger 3 is in large complexes in the center of the apical surface of proximal tubule-derived OK cells [J].
Akhter, S ;
Kovbasnjuk, O ;
Li, X ;
Cavet, M ;
Noel, J ;
Arpin, M ;
Hubbard, AL ;
Donowitz, M .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2002, 283 (03) :C927-C940
[5]   Inhibition of sodium/proton exchange by a Rab-GTPase-activating protein regulates endosomal traffic in yeast [J].
Ali, R ;
Brett, CL ;
Mukherjee, S ;
Rao, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) :4498-4506
[6]   Role of the cardiac Na+ /H+ exchanger during ischemia and reperfusion [J].
Allen, DG ;
Xiao, XH .
CARDIOVASCULAR RESEARCH, 2003, 57 (04) :934-941
[7]   Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].
Altschul, SF ;
Madden, TL ;
Schaffer, AA ;
Zhang, JH ;
Zhang, Z ;
Miller, W ;
Lipman, DJ .
NUCLEIC ACIDS RESEARCH, 1997, 25 (17) :3389-3402
[8]   Vacuolar cation/H+ exchange, ion homeostasis, and leaf development are altered in a T-DNA insertional mutant of AtNHX1, the Arabidopsis vacuolar Na+/H+ antiporter [J].
Apse, MP ;
Sottosanto, JB ;
Blumwald, E .
PLANT JOURNAL, 2003, 36 (02) :229-239
[9]   Salt tolerance conferred by overexpression of a vacuolar Na+/H+ antiport in Arabidopsis [J].
Apse, MP ;
Aharon, GS ;
Snedden, WA ;
Blumwald, E .
SCIENCE, 1999, 285 (5431) :1256-1258
[10]   Ion exchangers mediating NaCl transport in the renal proximal tubule [J].
Aronson, PS .
CELL BIOCHEMISTRY AND BIOPHYSICS, 2002, 36 (2-3) :147-153