A podocentric view of nephrology.
OBJECTIVE
The glomerular visceral epithelial cell plays a central role in ultrafiltration of the blood and in a wide variety of inherited and acquired diseases of the kidney. The discovery of nephrin and other slit diaphragm proteins has led to an explosion of knowledge in the biology of this cell type. The most significant recent discoveries are reviewed in this paper.


RESULTS
Together with the glomerular endothelial cells and intervening glomerular basement membrane, the podocyte constitutes a major portion of the glomerular filtration barrier that separates blood from the urinary space. A number of proteins have been identified that are localized to the slit diaphragms that separate podocyte foot processes. Although it has been suggested that the slit diaphragm represents the ultimate filtration barrier, additional roles for this structure as a signaling centre and in endocytosis have been identified. Mutations in genes that reside in the slit pore or interact with the actin cytoskeleton have been linked to a variety of inherited diseases of the podocyte. Additional mutations in these genes have been linked to sporadic forms of nephrotic syndrome and proposed as modifiers of renal risk. The generation of podocyte-specific transgenic models and genomic tools for the murine podocyte provide important resources for the glomerular biologist.


CONCLUSIONS
Over the past year, studies using human genetics, conditional gene targeting and cell biological approaches have led to a rapid increase in our understanding of podocyte and glomerular biology, which should lead to the development of novel therapies for individuals with glomerular disease.
Ly
Jo
J
The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Alexander
Mariam
M
Quaggin
Susan E
SE
D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D018390:Gene Targeting; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism*; D008565:Membrane Proteins; D011506:Proteins / Q000378:metabolism*
D008565:Membrane Proteins; D011506:Proteins; C113267:nephrin