RGD Reference Report - NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo. - Rat Genome Database

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NHE3 Na+/H+ exchanger supports proximal tubular protein reabsorption in vivo.

Authors: Gekle, M  Volker, K  Mildenberger, S  Freudinger, R  Shull, GE  Wiemann, M 
Citation: Gekle M, etal., Am J Physiol Renal Physiol. 2004 Sep;287(3):F469-73. Epub 2004 Apr 27.
RGD ID: 1581379
Pubmed: PMID:15113744   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00059.2004   (Journal Full-text)

Proximal tubular receptor-mediated endocytosis (RME) of filtered proteins prevents proteinuria. Pharmacological and genetic studies in cultured opossum kidney 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 S-3226 reduced the fractional reabsorption of [(14)C]cytochrome c by approximately 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 compared with 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 RME of filtered proteins in vivo.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
receptor-mediated endocytosis  IMP 1581379 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slc9a3  (solute carrier family 9 member A3)


Additional Information