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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wade, JB; Liu, J; Coleman, RA; Cunningham, R; Steplock, DA; Lee-Kwon, W; Pallone, TL; Shenolikar, S; Weinman, EJ

Published Date

  • December 2003

Published In

Volume / Issue

  • 285 / 6

Start / End Page

  • C1494 - C1503

PubMed ID

  • 12917102

Pubmed Central ID

  • 12917102

Electronic International Standard Serial Number (EISSN)

  • 1522-1563

International Standard Serial Number (ISSN)

  • 0363-6143

Digital Object Identifier (DOI)

  • 10.1152/ajpcell.00092.2003

Language

  • eng