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.
Tetsuro Takeda, Tammie McQuistan, Robert A. Orlando, Marilyn G. Farquhar
Title and authors | Publication | Year |
---|---|---|
Non-muscle myosins and the podocyte
M Noris, G Remuzzi |
Clinical Kidney Journal | 2012 |
The ADF/Cofilin-Pathway and Actin Dynamics in Podocyte Injury
B Teng, A Lukasz, M Schiffer |
International Journal of Cell Biology | 2012 |
The Gne M712T Mouse as a Model for Human Glomerulopathy
S Kakani, T Yardeni, J Poling, C Ciccone, T Niethamer, ED Klootwijk, I Manoli, D Darvish, S Hoogstraten-Miller, P Zerfas, E Tian, KG Hagen, JB Kopp, WA Gahl, M Huizing |
The American Journal of Pathology | 2012 |
Endothelin and the podocyte
M Barton, PL Tharaux |
Clinical Kidney Journal | 2012 |
Glycoprotein Hyposialylation Gives Rise to a Nephrotic-Like Syndrome That Is Prevented by Sialic Acid Administration in GNE V572L Point-Mutant Mice
M Ito, K Sugihara, T Asaka, T Toyama, T Yoshihara, K Furuichi, T Wada, M Asano |
PloS one | 2012 |
Membrane trafficking in podocyte health and disease
A Swiatecka-Urban |
Pediatric Nephrology | 2012 |
Deficits in sialylation impair podocyte maturation
B Weinhold, M Sellmeier, W Schaper, L Blume, B Philippens, E Kats, U Bernard, SP Galuska, H Geyer, R Geyer, K Worthmann, M Schiffer, S Groos, R Gerardy-Schahn, AK Münster-Kühnel |
Journal of the American Society of Nephrology : JASN | 2012 |
The anti-adhesive mucin podocalyxin may help initiate the transperitoneal metastasis of high grade serous ovarian carcinoma
JA Cipollone, ML Graves, M Köbel, SE Kalloger, T Poon, CB Gilks, KM McNagny, CD Roskelley |
Clinical & Experimental Metastasis | 2012 |
Puromycin aminonucleoside modulates p130Cas of podocytes
TS Ha, JY Choi, HY Park |
Korean Journal of Pediatrics | 2012 |
Rab27 effector Slp2-a transports the apical signaling molecule podocalyxin to the apical surface of MDCK II cells and regulates claudin-2 expression
T Yasuda, C Saegusa, S Kamakura, H Sumimoto, M Fukuda, A Nakano |
Molecular biology of the cell | 2012 |