podocalyxin

Podocalyxin, a sialoglycoprotein, is thought to be the major constituent of the glycocalyx of podocytes in the glomerulus (Bowman's capsule) in the kidneys. It is a member of the CD34 family of transmembrane sialomucins. It coats the secondary foot processes of the podocytes. It is negatively charged and thus functions through charge repulsion to keep adjacent foot processes separated, thereby keeping the urinary filtration barrier open. This function is further supported by knockout studies in mice which reveal an essential role in podocyte morphogenesis and a role in the opening of vascular lumens and regulation of vascular permeability. Of note, this is the only cell surface sialomucin knockout known to display a lethal phenotype.

Podocalyxin is also upregulated in a number of cancers and is frequently associated with poor prognosis. Podocalyxin is important for us to potentially provide a better understanding of cancer development and its aggressiveness through induced cell migration and the invasion from interacting with the actin-binding protein EZR. Effects of the EZR-dependent signaling events, among many other signal disturbances, can lead to increased activity in other vital pathways of cancer cells. Sialylated, O-glycosylated glycoforms of podocalyxin expressed by colon carcinoma cells possess L-selectin and E-selectin binding activity, and the affinity of the binding may be pivotal to the metastatic spread of colon carcinoma cells. At the cellular level podocalyxin has also been shown to regulate the size and topology of apical cell domains and act as a potent inducer of microvillus formation.