Localization and interaction of NHERF isoforms in the renal proximal tubule of the mouse

被引:90
作者
Wade, JB
Liu, J
Coleman, RA
Cunningham, R
Steplock, DA
Lee-Kwon, W
Pallone, TL
Shenolikar, S
Weinman, EJ
机构
[1] Univ Maryland, Dept Physiol, Sch Med, Baltimore, MD 21201 USA
[2] Univ Maryland, Dept Med, Sch Med, Baltimore, MD 21201 USA
[3] Dept Vet Affairs Med Ctr, Baltimore, MD 21201 USA
[4] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2003年 / 285卷 / 06期
关键词
NHE3; Npt2; ezrin; PDZ domains; immunolocalization;
D O I
10.1152/ajpcell.00092.2003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In expression systems and in yeast, Na/H exchanger regulatory factor ( NHERF)-1 and NHERF-2 have been demonstrated to interact with the renal brush border membrane proteins NHE3 and Npt2. In renal tissue of mice, however, NHERF-1 is required for cAMP regulation of NHE3 and for the apical targeting of Npt2 despite the presence of NHERF-2, suggesting another order of specificity. The present studies examine the subcellular location of NHERF-1 and NHERF-2 and their interactions with target proteins including NHE3, Npt2, and ezrin. The wild-type mouse proximal tubule expresses both NHERF-1 and NHERF-2 in a distinct pattern. NHERF-1 is strongly expressed in microvilli in association with NHE3, Npt2, and ezrin. Although NHERF-2 can be detected weakly in the microvilli, it is expressed predominantly at the base of the microvilli in the vesicle-rich domain. NHERF-2 appears to associate directly with ezrin and NHE3 but not Npt2. NHERF-1 is involved in the apical expression of Npt2 and the presence of other Npt2-binding proteins does not compensate totally for the absence of NHERF-1 in NHERF-1-null mice. Although NHERF-1 links NHE3 to the actin cytoskeleton through ezrin, the absence of NHERF-1 does not result in a generalized disruption of the architecture of the cell. Thus the mistargeting of Npt2 seen in NHERF-1-null mice likely represents a specific disruption of pathways mediated by NHERF-1 to achieve targeting of Npt2. These findings suggest that the organized subcellular distribution of the NHERF isoforms may play a role in the specific interactions mediating physiological control of transporter function.
引用
收藏
页码:C1494 / C1503
页数:10
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