Regulation of mouse podocyte process dynamics by protein tyrosine phosphata ses

Jochen Reiser, Fiona J. Pixley, Andreas Hug, Wilhelm Kriz, William E. Smoyer, E. Richard Stanley, Peter Mundel

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Background. Effacement of podocyte foot processes occurs early in many glomerular diseases associated with proteinuria and is accompanied by a reorganization of the actin cytoskeleton. The molecular mechanisms regulating these structural changes are poorly understood. Methods. To address these questions, we analyzed the effect of the polycation, protamine sulfate (PS), and puromycin aminonucleoside (PA) on the morphology, cytoskeleton, and tyrosine phosphorylation of differentiated process-bearing cultured podocytes. Results. PS and PA induced similar profound morphological alterations, including retraction and detachment of podocyte processes from the extracellular matrix (ECM). The effects of PS occurred within six hours, whereas PA showed its most severe effects after 72 hours. Structural changes included reorganization of the actin cytoskeleton and focal contacts and were accompanied by an increase in tyrosine phosphorylation. The same effects were induced by application of vanadate, an inhibitor of protein tyrosine phosphatases (PTPs), suggesting that PTPs regulate podocyte process structure. Since disruption of the actin cytoskeleton with cytochalasin B protected the cells from PS-induced effacement and detachment, cytoplasmic PTPs were implicated in these events. Using reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated the expression of four cytoplasmic PTPs in podocytes: SHP-2, PTP-PEST, PTP-1B, and PTP-36. Conclusions. These studies indicate an important role for cytoplasmic PTPs as regulators of podocyte process dynamics. Future studies will aim at restoring the normal foot process architecture of podocytes in glomerular diseases associated with proteinuria by modulating the activity of cytoplasmic PTPs.

Original languageEnglish (US)
Pages (from-to)2035-2042
Number of pages8
JournalKidney International
Issue number5
StatePublished - 2000
Externally publishedYes


  • Focal contacts
  • Nephrotic syndrome
  • Protamine sulfate
  • Puromycin aminonucleoside

ASJC Scopus subject areas

  • Nephrology


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