RGD Reference Report - Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. - Rat Genome Database

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Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton.

Authors: Takeda, T  McQuistan, T  Orlando, RA  Farquhar, MG 
Citation: Takeda T, etal., J Clin Invest 2001 Jul;108(2):289-301.
RGD ID: 634171
Pubmed: PMID:11457882   (View Abstract at PubMed)
PMCID: PMC203027   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI12539   (Journal Full-text)

Podocalyxin (PC), the major sialoprotein of glomerular epithelial cells (GECs), helps maintain the characteristic architecture of the foot processes and the patency of the filtration slits. PC associates with actin via ezrin, a member of the ERM family of cytoskeletal linker proteins. Here we show that PC is linked to ezrin and the actin cytoskeleton via Na(+)/H(+)-exchanger regulatory factor 2 (NHERF2), a scaffold protein containing two PDZ (PSD-95/Dlg/ZO-1) domains and an ERM-binding region. The cytoplasmic tail of PC contains a C-terminal PDZ-binding motif (DTHL) that binds to the second PDZ domain of NHERF2 in yeast two-hybrid and in vitro pull-down assays. By immunocytochemistry NHERF2 colocalizes with PC and ezrin along the apical domain of the GEC plasma membrane. NHERF2 and ezrin form a multimeric complex with PC, as they coimmunoprecipitate with PC. The PC/NHERF2/ezrin complex interacts with the actin cytoskeleton, and this interaction is disrupted in GECs from puromycin aminonucleoside-, protamine sulfate-, or sialidase-treated rats, which show a dramatic loss of foot processes, comparable to that seen in the nephrotic syndrome. Thus NHERF2 appears to function as a scaffold protein linking PC to ezrin and the actin cytoskeleton. PC/NHERF2/ezrin/actin interactions are disrupted in pathologic conditions associated with changes in GEC foot processes, indicating their importance for maintaining the unique organization of this epithelium.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
apical plasma membrane located_inIDA 634171; 634171; 634171PMID:11457882UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Asic3  (acid sensing ion channel subunit 3)
Ezr  (ezrin)
Nherf1  (NHERF family PDZ scaffold protein 1)
Nherf2  (NHERF family PDZ scaffold protein 2)
Podxl  (podocalyxin-like)


Additional Information