Pdpn
Developmental stage
Expressed in mesenteric lymphatic endothelial cells at 16.5 and 18.5 dpc (at protein level) (PubMed:28179430). At 12.5 dpc and 13.5 dpc is expressed in the endothelial cells of forming lymph sacs (PubMed:20110424).
Domain
The cytoplasmic domain controls FRC elongation but is dispensable for contraction (PubMed:25347465). The cytoplasmic domain is essential for recruitment to invadopodia and ECM degradation (By similarity).
Function
Mediates effects on cell migration and adhesion through its different partners. During development plays a role in blood and lymphatic vessels separation by binding CLEC1B, triggering CLEC1B activation in platelets and leading to platelet activation and/or aggregation (PubMed:14522983, PubMed:15231832, PubMed:17616532, PubMed:20110424). Interaction with CD9, on the contrary, attenuates platelet aggregation and pulmonary metastasis induced by PDPN. Mediates effects on cell migration and adhesion through its different partners. Through MSN or EZR interaction promotes epithelial-mesenchymal transition (EMT) leading to ERZ phosphorylation and triggering RHOA activation leading to cell migration increase and invasiveness. Interaction with CD44 promotes directional cell migration in epithelial and tumor cells (By similarity). In lymph nodes (LNs), controls 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 through association with unknown transmembrane proteins. Engagement of CLEC1B by PDPN promotes FRCs relaxation by blocking lateral membrane interactions leading to reduction of ERM proteins (EZR; MSN and RDX) and MYL9 activation (PubMed:25347465). Through binding with LGALS8 may participate in connection of the lymphatic endothelium to the surrounding extracellular matrix (By similarity). In keratinocytes, induces changes in cell morphology showing an elongated shape, numerous membrane protrusions, major reorganization of the actin cytoskeleton, increased motility and decreased cell adhesion (PubMed:10574709). Controls invadopodia stability and maturation leading to efficient degradation of the extracellular matrix (ECM) in tumor cells through modulation of RHOC activity in order to activate ROCK1/ROCK2 and LIMK1/LIMK2 and inactivation of CFL1 (By similarity). Required for normal lung cell proliferation and alveolus formation at birth (PubMed:12654292). Does not function as a water channel or as a regulator of aquaporin-type water channels (By similarity). Does not have any effect on folic acid or amino acid transport (PubMed:12032185).
Post-translational modifications
Extensively O-glycosylated. Contains sialic acid residues. O-glycosylation is necessary for platelet aggregation activity. Disialylated at Thr-52; sialic acid is critical for platelet-aggregating activity and for CLEC1B interaction (By similarity).
Phosphorylated by PKA; decreases cell migration.
The N-terminus is blocked.
Sequence Similarities
Belongs to the podoplanin family.
Tissue Specificity
Detected at high levels in lung and brain, at lower levels in kidney, stomach, liver, spleen and esophagus, and not detected in skin and small intestine. Expressed in epithelial cells of choroid plexus, ependyma, glomerulus and alveolus, in mesothelial cells and in endothelia of lymphatic vessels. Also expressed in stromal cells of peripheral lymphoid tissue and thymic epithelial cells. Detected in carcinoma cell lines and cultured fibroblasts. Expressed at higher levels in colon carcinomas than in normal colon tissue.
Cellular localization
- Membrane
- Single-pass type I membrane protein
- Cell projection
- Lamellipodium membrane
- Single-pass type I membrane protein
- Cell projection
- Filopodium membrane
- Single-pass type I membrane protein
- Cell projection
- Microvillus membrane
- Single-pass type I membrane protein
- Cell projection
- Ruffle membrane
- Single-pass type I membrane protein
- Membrane raft
- Apical cell membrane
- Basolateral cell membrane
- Cell projection
- Invadopodium
- Localized to actin-rich microvilli and plasma membrane projections such as filopodia, lamellipodia and ruffles (PubMed:10574709). Association to the lipid rafts is required for PDPN-induced epithelial to mesenchymal transition (EMT). Colocalizes with CD9 in tetraspanin microdomains. Localized at invadopodium adhesion rings in tumor cell. Association to the lipid rafts is essential for PDPN recruitment to invadopodia and ECM degradation (By similarity).
Alternative names
Gp38, Ots8, Pdpn, Podoplanin, Glycoprotein 38, OTS-8, PA2.26 antigen, Transmembrane glycoprotein E11, E11