Cyclin-dependent kinase 5 is a regulator of podocyte differentiation, proliferation, and morphology.
Podocytes are highly specialized and terminally differentiated glomerular cells that play a vital role in renal physiology, including the prevention of proteinuria. Cyclin-dependent kinase 5 (CDK5) has been shown to influence several cellular processes in other terminally differentiated cells, in particular neurons. In this study, we examined the role of CDK5 in podocyte differentiation, proliferation, and morphology. In conditionally immortalized mouse podocytes in culture, CDK5 increased in association with podocyte differentiation. During mouse glomerulogenesis in vivo, CDK5 expression was predominantly detected in podocytes from the capillary loop stage to maturation and persisted in the podocytes of adult glomeruli. In contrast, CDK5 was markedly decreased in the proliferating and dedifferentiated podocytes of mice with anti-glomerular basement membrane nephritis and in human immunodeficiency virus transgenic mice. p35, the activator of CDK5, was also detected in podocytes and the p35/CDK5 complex was active. Cell fractionation studies showed that active p35/CDK5 was mainly localized to the plasma membrane. Specific inhibition of CDK5 in differentiated cultured podocytes, either pharmacologically or with siRNA, induced shape changes, with cellular elongation and loss of process formation compared to the characteristic arborized phenotype. These data suggest a role for CDK5 as a regulator of podocyte differentiation, proliferation, and morphology.
Department of Medicine, Division of Nephrology, University of Washington School of Medicine, Box 356521, Seattle, WA 98195, USA.
Sian V
SV
Griffin
Keiju
K
Hiromura
Jeffrey
J
Pippin
Arndt T
AT
Petermann
Mary J
MJ
Blonski
Ron
R
Krofft
Satoru
S
Takahashi
Ashok B
AB
Kulkarni
Stuart J
SJ
Shankland
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology*; D005455:Fluorescent Antibody Technique; D007674:Kidney Diseases / Q000201:enzymology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology* / Q000201:enzymology* / Q000254:growth & development; D051379:Mice; D010770:Phosphotransferases; D011506:Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction
C492236:Cdk5r1 protein, mouse; D011506:Proteins; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases