Podoplanin is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''PDPN''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Structure and function
Podoplanin is a
mucin
Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...
-type protein with a mass of 36- to 43-kDa. It is relatively well conserved between species, with homologues in humans, mice, rats, dogs and hamsters.
This gene encodes a type-I, integral membrane, heavily O-
glycosylated
Glycosylation is the reaction in which a carbohydrate (or 'glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not alw ...
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
with diverse distribution in human tissues. The physiological function of this protein may be related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor. The specific function of this protein has not been determined but it has been proposed as a marker of lung injury. Alternatively spliced transcript variants encoding different isoforms have been identified.
This protein has been found to have functions in lung alveolar cells, kidney podocytes, and lymphatic endothelial cells. More recently, this protein has been found in neural tissue in both mouse and human samples.
In lymphatic endothelial cells, experimentation has indicated that podoplanin plays a role in proper formation of linkages between the cardiovascular system and the lymphatic systems, typically causing fatty liver disease in these mice.
Although the exact function is unknown in many tissues, podoplanin is generally receptive to detection via immunofluorescent staining and has been shown to co-localize with the protein
nestin, a type VI intermediate filament protein expressed almost primarily in neural tissues.
Currently, the only protein known to interact with podoplanin physiologically is
CLEC-2
C-type lectin domain family 1 member B is a protein that in humans is encoded by the ''CLEC1B'' gene.
Natural killer (NK) cells express multiple calcium-dependent (C-type) lectin-like receptors, such as CD94 (KLRD1; MIM 602894) and NKG2D (KLRC4; ...
, a C-type lectin 2 expressed on platelets and on
hematopoietic cell
A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), a ...
s. Both serve a role in the proper formation of blood/lymphatic connections in embryonic development.
Clinical significance
PDPN has been studied extensively in the cancer field. It is a specific lymphatic vessel marker, and since lymphangiogenesis levels are correlated with poor prognosis in cancer patients, it can be used as a diagnostic marker.
It is often upregulated in certain types of cancer, including several types of
squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
s, malignant
mesothelioma
Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining ...
and
brain tumor
A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and seconda ...
s.
Moreover, it can be upregulated by cancer-associated fibroblasts (CAFs) in the tumor stroma,
where it has been associated with poor prognosis.
In squamous cell carcinomas, PDPN is believed to play a key role in the cancer cell invasiveness by controlling
invadopodia
Invadopodia are actin-rich protrusions of the plasma membrane that are associated with degradation of the extracellular matrix in cancer invasiveness and metastasis. Very similar to podosomes, invadopodia are found in invasive cancer cells and are ...
, and thus mediating efficient
ECM degradation.
References
Further reading
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External links
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* {{PDBe-KB2, Q62011, Mouse Podoplanin