title: Cortactin interacts with podocalyxin and mediates morphological change of podocytes through its phosphorylation.
abstract: OBJECTIVE
  Morphological change of podocytes is closely correlated with the development of proteinuria. Podocalyxin is a major sialoglycoprotein of the podocytes and is thought to be involved in the maintenance of the foot processes structure. Our aim was to examine the mechanism by which podocalyxin contributes to the morphological change of podocytes.
  
  
  METHODS
  We searched protein(s) which coprecipitate with podocalyxin using rat glomerular lysate. Localization of podocalyxin and the coprecipitated protein, cortactin, was studied in a model of puromycin aminonucleoside (PAN) nephrosis by immunocytochemistry. Tyrosine phosphorylation of cortactin was examined. Association of the podocalyxin/cortactin complex with the actin cytoskeleton was evaluated by extraction with Triton-X and immunoblotting.
  
  
  RESULTS
  Cortactin was found to be co-immunoprecipitated with podocalyxin. Immunocytochemical analysis revealed that these 2 proteins colocalized in the apical side of podocytes. In PAN nephrosis, localization of cortactin was altered after the onset of proteinuria, with increased tyrosine phosphorylation. Simultaneously, the dissociation of the podocalyxin/cortactin complex from the actin cytoskeleton was induced.
  
  
  CONCLUSIONS
  These results indicate that cortactin mediates interaction between podocalyxin and actin filaments in podocytes and that alteration of this interaction may play a role in the process of morphological change of podocytes.
authors.affiliation: Discovery Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. tatsuo.kobayashi@shionogi.co.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Notoya
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shinosaki
authors.forename: Hidetake
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000818:Animals; D051356:Cortactin / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D009401:Nephrosis / Q000139:chemically induced / Q000378:metabolism; D010766:Phosphorylation; D050199:Podocytes / Q000166:cytology / Q000187:drug effects*; D011507:Proteinuria / Q000209:etiology; D011692:Puromycin Aminonucleoside; D051381:Rats; D017208:Rats, Wistar; D012795:Sialoglycoproteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D051356:Cortactin; D012795:Sialoglycoproteins; C001643:podocalyxin; D011692:Puromycin Aminonucleoside