Cortactin interacts with podocalyxin and mediates morphological change of podocytes through its phosphorylation.
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.
Kobayashi
Tatsuo
T
Discovery Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan. tatsuo.kobayashi@shionogi.co.jp
Notoya
Mitsuru
M
Shinosaki
Toshihiro
T
Kurihara
Hidetake
H
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*
D051356:Cortactin; D012795:Sialoglycoproteins; C001643:podocalyxin; D011692:Puromycin Aminonucleoside