| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Physiologisches Institut, University of Wuerzburg, Wuerzburg, Germany
2 Department of Molecular Genetics, Biochemistry, and Microbiology, The University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
3 Physiologisches Institut, University of Duisburg-Essen, Essen, Germany
* To whom correspondence should be addressed. E-mail: michael.gekle{at}mail.uni-wuerzburg.de.
Proximal tubular receptor-mediated endocytosis (RME) of filtered proteins prevents proteinuria. Pharmacological and genetic studies in cultured OK cells have shown that the apical Na+/H+ exchanger isoform 3 (NHE3) supports RME by interference with endosomal pH homeostasis and endocytic fusion events. However, it is not known whether NHE3 also supports proximal tubular RME in vivo. We analyzed proximal tubular protein reabsorption by microinfusion experiments in rats and investigated renal protein excretion in NHE3 knockout (Nhe3-/-) mice. Inhibition of NHE3 by EIPA or S3226 reduced the fractional reabsorption of 14C-cytochrome C by ~50% during early proximal microinfusion. During early distal microinfusion no protein reabsorption could be detected. Urinary protein excretion of Nhe3-/- or heterozygous mutant mice was significantly higher as compared to wild-type mice. SDS-PAGE analysis of urinary proteins revealed that Nhe3-/- animals excreted proteins the size of albumin or smaller. Thus, a reduction in NHE3 activity or abundance causes tubular proteinuria. These data show that NHE3 supports proximal tubular receptor-mediated endocytosis of filtered proteins in vivo.
This article has been cited by other articles:
|
|
 |
|
  R. T. Alexander and S. Grinstein Tethering, recycling and activation of the epithelial sodium-proton exchanger, NHE3 J. Exp. Biol., June 1, 2009; 212(11): 1630 - 1637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. K. Hoffmann, I. H. Lambert, and S. F. Pedersen Physiology of Cell Volume Regulation in Vertebrates Physiol Rev, January 1, 2009; 89(1): 193 - 277. [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]
|
|
|
|
 |
|
 N. A. Kassem, R. Deane, M. B. Segal, and J. E. Preston Role of transthyretin in thyroxine transfer from cerebrospinal fluid to brain and choroid plexus Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1310 - R1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ludwig, B. Utsch, and L. A. H. Monnens Recent advances in understanding the clinical and genetic heterogeneity of Dent's disease Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2708 - 2717. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang, H. Cai, L. Cebotaru, D. H. Hryciw, E. J. Weinman, M. Donowitz, S. E. Guggino, and W. B. Guggino ClC-5: role in endocytosis in the proximal tubule Am J Physiol Renal Physiol, October 1, 2005; 289(4): F850 - F862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Jentsch Chloride Transport in the Kidney: Lessons from Human Disease and Knockout Mice J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1549 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Brett, M. Donowitz, and R. Rao Evolutionary origins of eukaryotic sodium/proton exchangers Am J Physiol Cell Physiol, February 1, 2005; 288(2): C223 - C239. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
