Podocalyxin, a
sialoglycoprotein, is thought to be the major constituent of the
glycocalyx
The glycocalyx (: glycocalyces or glycocalyxes), also known as the pericellular matrix and cell coat, is a layer of glycoproteins and glycolipids which surround the cell membranes of bacteria, epithelial cells, and other cells.
Animal epithe ...
of
podocytes
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 ...
in the
glomerulus
''Glomerulus'' (; : glomeruli) is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn".
''Glomerulus'' may refer to ...
(
Bowman's capsule
Bowman's capsule (or the Bowman capsule, capsula glomeruli, or glomerular capsule) is a cup-like sac at the beginning of the Renal tubule, tubular component of a nephron in the mammalian kidney that performs the first step in the filtration of b ...
) in the kidneys.
[Omim - Podocalyxin-Like; Podxl](_blank)
/ref> It is a member of the CD34
CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species.
CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first desc ...
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
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...
cells possess L-selectin
L-selectin, also known as CD62L, is a cell adhesion molecule found on the cell surface of leukocytes, and the blastocyst. It is coded for in the human by the ''SELL'' gene. L-selectin belongs to the selectin family of proteins, which recognize si ...
and E-selectin
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a selectin cell adhesion molecule expressed only on endotheli ...
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.
Podocalyxin is also known as TRA-1-60 and is a marker of pluripotent stem cells.
Discussion
Podocalyxin has been found to possess post a few translational modification events and likely has more to be discovered. There are Glycosylated O-linked events with the amino acid Serine at position 144, and two N-linked glycosylation events with Asparagine at positions 193 and 395. Along with phosphorylation residues at positions 570 and 596 with Serine. The composition of the Podocalyxin transmembrane protein consists of acidic residues from position 162–192, many polar residues at positions 200–219, 230–267, and 554–568, as well as containing both basic and acidic residues from position 590–605.
It has been found that the length of the protein is 605 amino acids and has a mass of about 65,076 daltons. The structure consists of topological domains at position 33-500 being extracellular and position 522-605 being cytoplasmic. The transmembrane domain is helical in structure at position 501–521.
To go further in our understanding about this protein in understanding the pathology of mutagenesis could help biotech companies and the medical industry tremendously, as could growing our current knowledge of all proteins especially those relating to developments in cancer. Currently there are known mutation events at positions 97, 118, and 124 on the extracellular region of the protein likely altering protein structure and transduction signaling not invoking a correct bodily response.
See also
*Cell signaling
In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...
*Cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
References
{{Reflist
Single-pass transmembrane proteins