PDPN
Description
The PDPN (podoplanin) is a protein-coding gene located on chromosome 1.
Podoplanin is a protein that in humans is encoded by the PDPN gene. Podoplanin is a mucin-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 glycoprotein 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.
PDPN, also known as Aggrus, Glycoprotein 36, PA2.26 antigen, and T1-alpha, mediates effects on cell migration and adhesion through interactions with various partners. During development, PDPN plays a role in separating blood and lymphatic vessels by binding CLEC1B, triggering its activation in platelets and leading to platelet activation or aggregation. Conversely, interaction with CD9 attenuates platelet aggregation induced by PDPN. PDPN promotes epithelial-mesenchymal transition (EMT) through its interactions with MSN or EZR, leading to ERZ phosphorylation and RHOA activation, ultimately increasing cell migration and invasiveness. Interaction with CD44 promotes directional cell migration in epithelial and tumor cells. In lymph nodes, PDPN regulates fibroblastic reticular cells (FRCs) adhesion to the extracellular matrix (ECM) and contraction of the actomyosin by maintaining ERM proteins (EZR, MSN, and RDX) and MYL9 activation. Engagement of CLEC1B by PDPN promotes FRCs relaxation by blocking lateral membrane interactions, leading to a reduction in ERM proteins and MYL9 activation. PDPN may participate in connecting the lymphatic endothelium to the surrounding extracellular matrix through its binding with LGALS8. In keratinocytes, PDPN induces changes in cell morphology, resulting in an elongated shape, numerous membrane protrusions, a major reorganization of the actin cytoskeleton, increased motility, and decreased cell adhesion. PDPN controls invadopodia stability and maturation, leading to efficient degradation of the ECM in tumor cells by modulating RHOC activity to activate ROCK1/ROCK2 and LIMK1/LIMK2 and inactivate CFL1. PDPN is required for normal lung cell proliferation and alveolus formation at birth. It does not function as a water channel or a regulator of aquaporin-type water channels and does not have any effect on folic acid or amino acid transport. PDPN exists as a homodimer and interacts with CLEC1B, CD9, LGALS8, HSPA9, CD44, MSN, EZR, and CCL21.
PDPN is also known as AGGRUS, D2-40, GP36, GP40, Gp38, HT1A-1, OTS8, PA2.26, T1A, T1A-2, T1A2, TI1A.
