Podocytes (also known as visceral epithelial cells) are highly specialized cells found in the glomeruli of kidney nephrons. Podocytes wrap the external surface of the basal lamina of the glomerular capillaries (Figure 1). The morphology of podocytes is very complex, and their main role related to the filtration of the blood plasma, which happens in the kidney glomeruli.
Podocytes are really morphologically complex cells (Figure 2). They are polarized cells, with an apical domain toward the Bowman's capsule and a basal domain toward the basal lamina of the capillary endothelium. Podocytes show a flat cytoplasm with a visible rise containing the nucleus. They have a well-developed Golgi apparatus, abundant endoplasmic reticulum, and many mitochondria and lysosomes. The cytoplasm sends many tiny finger-like protrusions that wrap the basal lamina of capillaries. These protrusions are called intergidital processes because protrusions coming from adjoining podocytes may be intermingled. The organelles are scarce in the interdigital processes. The form and length of these little expansions depend on the actin filaments. Neighbor interdigital processes are connected by molecular complexes known as slit diaphragms, and the membrane shows a dense glycocalyx with a negative net charge, which make interdigital processes not to touch one another. Thus, their distribution on the surface of capillaries is rather homogeneous. Diaphragm slits are about 30 a 40 nm in length, looking like adherent junctions (with a dense region). They contain cadherins, ZO-1 protein, nephrin, FAT and NEPH-1 proteins.
Podocytes are attached to the basal lamina by alpha3-beta1 integrins and by distroglycans. Both molecules are also connected to actin filaments in the cytoplasm. Cytoskeleton is responsible for the connection between of neighboring interdigital processes through the slit diaphragms.
Podocytes are generated during the kidney formation by messenchymal cell differentiation. These messenchymal cells also differentiate into the Bowman's capsule cells and the rest of the cells of the glomerulus, including endothelial and mesangial cells. Initially, podocytes are polygonal cells connected by gap junctions. However, when capillaries are developing, podocytes change the morphology to wrap those capillaries, lose gap-junctions and express specific molecules like synaptopodin, as well as the intermediate filament vimentin. The WT-1 protein is characteristic of podocytes both during development and at adult functional stage.
Unlike the mesangial cells of the glomerulus, the division rate of podocytes is very low. It makes sense because podocyte divisions may disturb the glomerulus organization and therefore its filtering capacity. Most podocytes are in a steady state maintained by a constant synthesis of mitotic inhibitors. Podocytes are not able to replace other dead podocytes or cover enlargements of the capillary basal lamina with new cells. Experimentally, podocytes can be induced to proliferate. However, only the nucleus is divided and there is no cytokinesis. The decrease in the number of podocytes in a glomerulus is compensated by increasing the cell expansions of the already present podocytes.
Podocytes are involved in the filtration of the blood plasma that takes place in the glomerulus. They are also important for preserving the structure of the glomerulus. Together with the endothelium and the basal lamina, podocytes are the third component of the filtration barrier. This barrier selects molecules according to their size and electrical charge, so that large molecules and ions are not allowed to cross. The less selective part of the barrier is the diaphragm slit between the interdigital processes of podocytes.
Podocytes contribute to the basal lamina by synthesizing and releasing some of its components. Basal lamina contains type IV collagen, laminin, entactin, agrin and perlecan. It is in permanent renewing, and this is essential for filtering. Therefore, podocytes are also responsible for the filtration capability of the basal lamina. Furthermore, failures in interdigital processes led to filtering flaws and some pathologies like proteinuria.
The mechanical resistance of podocytes withstands the hydraulic pressure of blood in capillaries, avoiding the breakage or distortion of the blood vessels. The mechanical strength is provided by the interdigital processes, which contain a cytoskeleton made up of mainly actin filament that is connected to the basal lamina through integrins. The ability of actin/myosin for producing contractions make adjustable the intensity and pressure of the wrapping around the capillaries, which also influences the filtration capacity.
Pavenstädt H, Kriz W, Kretzler M. 2003. Cell biology of the glomerular podocyte. Physiologycal reviews 83: 253-307.