Podocalyxin-like protein 1 is a protein that in humans is encoded by the PODXL gene. [3]
Podocalyxin-like protein 1 is a protein that in humans is encoded by the PODXL gene. [3]
This gene encodes a member of the CD34 sialomucin protein family. [4] The encoded protein was originally identified as an important component of glomerular podocytes. Inactivation of the encoding gene in mice leads to anuria, omphalocele and perinatal death. [5] Podocytes are highly differentiated epithelial cells with interdigitating foot processes covering the outer aspect of the glomerular basement membrane. Other biological activities of the encoded protein include: binding in a membrane protein complex with Na+/H+ exchanger regulatory factor to intracellular cytoskeletal elements, playing a role in hematopoietic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin. [3]
The expression and localisation of PODXL in human cells, tissues and organs have been investigated by the Human Protein Atlas consortium. [6] According to antibody-based profiling, the protein is present in glomerular podocytes, endothelial cells, glandular cells in fallopian tube, uterus and seminal vesicle and according to RNA expression analysis, the PODXL transcripts are present in all analysed human tissues. [7] Based on confocal microscopy, [8] the protein is mainly localised to the plasma membrane and microtubule organizing center and in addition localized to vesicles. [9]
PODXL has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2. [10] [11] [12]
Podocalyxin is upregulated in a number of cancers and is frequently associated with poor prognosis. [13] Based on patient survival data, [14] high level of PODXL transcripts in tumor cells is associated with poor prognosis in renal cancer.
Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule filters the blood, retaining large molecules such as proteins while smaller molecules such as water, salts, and sugars are filtered as the first step in the formation of urine. Although various viscera have epithelial layers, the name visceral epithelial cells usually refers specifically to podocytes, which are specialized epithelial cells that reside in the visceral layer of the capsule. One type of specialized epithelial cell is podocalyxin.
CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.
Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is a transmembrane protein that is a structural component of the slit diaphragm. They are present on the tips of the podocytes as an intricate mesh and convey strong negative charges which repel protein from crossing into the Bowman's space.
Podocalyxin, a sialoglycoprotein, is thought to be the major constituent of the glycocalyx of podocytes in the glomerulus 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.
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Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 is an enzyme that in humans is encoded by the MAGI1 gene.
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Synaptopodin is a protein that in humans is encoded by the SYNPO gene.
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Inhibitor of growth protein 4 is a protein that in humans is encoded by the ING4 gene.
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