| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print January 8, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00131.2001
Submitted on April 26, 2001
Accepted on January 2, 2002
1 Pediatrics, University of Michigan, Ann Arbor, MI, USA
2 Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: dkershaw{at}umich.edu.
The transmembrane sialoglycoprotein podocalyxin is thought to be essential in the fine interdigitating foot process structure of the podocyte. The intracellular carboxyl terminal amino acids Asp-Thr-His-Leu (DTHL), of podocalyxin comprise a putative ligand for a type I PDZ domain. A 20 amino acid synthetic peptide containing this motif was used to screen a cDNA library and clones of rabbit Na+/H+ exchange regulatory factor-2 (NHERF-2) were obtained. In vitro analysis demonstrated that each PDZ domain of NHERF-2 could bind podocalyxin independently. NHERF-2 coprecipitated from glomerular extracts with podocalyxin, and podocalyxin and NHERF-2 co-localized in the glomerular capillary loops indicating that podocalyxin and NHERF-2 may interact in vivo. Podocalyxin peptide missing the terminal leucine (DTH-) failed to interact with NHERF-2 in vitro. Podocalyxin localized to the apical membrane of transfected MDCK cells. However, mutant podocalyxin (missing a functional DTHL carboxyl terminal motif) showed cytoplasmic and apical membrane localization in transfected cells and was also less stable at the apical membrane as assessed by confocal microscopy and biotinylation studies. Mutant podocalyxin did lower the transepithelial resistance of MDCK cell monolayers, albeit to a lesser extent than full-length podocalyxin. We conclude podocalyxin can interact with both PDZ domains of NHERF-2 and this interaction requires the intact carboxyl terminus of podocalyxin, which is also responsible for the efficient apical localization of podocalyxin in transfected MDCK cells. These results suggest that the interaction of podocalyxin with NHERF-2 may function to efficiently retain podocalyxin at the apical surface of the podocyte and provide a mechanism linking podocalyxin to the actin cytoskeleton.
This article has been cited by other articles:
|
|
 |
|
  J. S. Nielsen and K. M. McNagny The Role of Podocalyxin in Health and Disease J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1669 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Overgaard, K. M. Sanzone, K. S. Spiczka, D. R. Sheff, A. Sandra, and C. Yeaman Deciliation Is Associated with Dramatic Remodeling of Epithelial Cell Junctions and Surface Domains Mol. Biol. Cell, January 1, 2009; 20(1): 102 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Nielsen and K. M. McNagny Novel functions of the CD34 family J. Cell Sci., November 15, 2008; 121(22): 3683 - 3692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Y. Yu, J.-Y. Chen, Y.-Y. Lin, K.-F. Shen, W.-L. Lin, C.-L. Chien, M. B.A. ter Beest, and T.-S. Jou A Bipartite Signal Regulates the Faithful Delivery of Apical Domain Marker Podocalyxin/Gp135 Mol. Biol. Cell, May 1, 2007; 18(5): 1710 - 1722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Harita, N. Miyauchi, T. Karasawa, K. Suzuki, G. D. Han, H. Koike, T. Igarashi, F. Shimizu, and H. Kawachi Altered expression of junctional adhesion molecule 4 in injured podocytes Am J Physiol Renal Physiol, February 1, 2006; 290(2): F335 - F344. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Cheng, Y.-Y. Lin, C.-Y. Yu, J.-Y. Chen, K.-F. Shen, W.-L. Lin, H.-K. Liao, Y.-J. Chen, C.-H. Liu, V. F. Pang, et al. Molecular Identification of Canine Podocalyxin-Like Protein 1 as a Renal Tubulogenic Regulator J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1612 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Meder, A. Shevchenko, K. Simons, and J. Fullekrug Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells J. Cell Biol., January 17, 2005; 168(2): 303 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Shenolikar, J. W. Voltz, R. Cunningham, and E. J. Weinman Regulation of Ion Transport by the NHERF Family of PDZ Proteins Physiology, December 1, 2004; 19(6): 362 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Schmieder, M. Nagai, R. A. Orlando, T. Takeda, and M. G. Farquhar Podocalyxin Activates RhoA and Induces Actin Reorganization through NHERF1 and Ezrin in MDCK Cells J. Am. Soc. Nephrol., September 1, 2004; 15(9): 2289 - 2298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B. Wade, J. Liu, R. A. Coleman, R. Cunningham, D. A. Steplock, W. Lee-Kwon, T. L. Pallone, S. Shenolikar, and E. J. Weinman Localization and interaction of NHERF isoforms in the renal proximal tubule of the mouse Am J Physiol Cell Physiol, December 1, 2003; 285(6): C1494 - C1503. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
