title: Regulation of mouse podocyte process dynamics by protein tyrosine phosphatases rapid communication.
abstract: 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.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: J
authors.initials: J
authors.lastname: Reiser
authors.forename: F J
authors.initials: FJ
authors.lastname: Pixley
authors.forename: A
authors.initials: A
authors.lastname: Hug
authors.forename: W
authors.initials: W
authors.lastname: Kriz
authors.forename: W E
authors.initials: WE
authors.lastname: Smoyer
authors.forename: E R
authors.initials: ER
authors.lastname: Stanley
authors.forename: P
authors.initials: P
authors.lastname: Mundel
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D007678:Kidney Glomerulus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D011479:Protamines / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology
chemical_list: D000199:Actins; D011479:Protamines; D014638:Vanadates; D014443:Tyrosine; D011692:Puromycin Aminonucleoside; D017027:Protein Tyrosine Phosphatases