Podoplanin is a protein that in humans is encoded by the PDPN gene.[5][6][7]

PDPN
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPDPN, AGGRUS, GP36, GP40, Gp38, HT1A-1, OTS8, PA2.26, T1A, T1A-2, T1A2, TI1A, podoplanin, D2-40
External IDsOMIM: 608863; MGI: 103098; HomoloGene: 4729; GeneCards: PDPN; OMA:PDPN - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001290822
NM_010329

RefSeq (protein)

NP_001006625
NP_001006626
NP_006465
NP_938203

NP_001277751
NP_034459

Location (UCSC)Chr 1: 13.58 – 13.62 MbChr 4: 142.99 – 143.03 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Structure and function

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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.[8]

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.[7]

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.[9]

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.[9]

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.[10] Currently, the only protein known to interact with podoplanin physiologically is CLEC-2, a C-type lectin 2 expressed on platelets and on hematopoietic cells.[11] Both serve a role in the proper formation of blood/lymphatic connections in embryonic development.

Clinical significance

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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.[8] It is often upregulated in certain types of cancer, including several types of squamous cell carcinomas, malignant mesothelioma and brain tumors.[8] Moreover, it can be upregulated by cancer-associated fibroblasts (CAFs) in the tumor stroma,[8][12] where it has been associated with poor prognosis.[13]

In squamous cell carcinomas, PDPN is believed to play a key role in the cancer cell invasiveness by controlling invadopodia, and thus mediating efficient ECM degradation.[14]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162493Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028583Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Zimmer G, Oeffner F, Von Messling V, Tschernig T, Gröness HJ, Klenk HD, Herrler G (July 1999). "Cloning and characterization of gp36, a human mucin-type glycoprotein preferentially expressed in vascular endothelium". The Biochemical Journal. 341 ( Pt 2) (Pt 2): 277–84. doi:10.1042/0264-6021:3410277. PMC 1220357. PMID 10393083.
  6. ^ Ma T, Yang B, Matthay MA, Verkman AS (July 1998). "Evidence against a role of mouse, rat, and two cloned human t1alpha isoforms as a water channel or a regulator of aquaporin-type water channels". American Journal of Respiratory Cell and Molecular Biology. 19 (1): 143–9. doi:10.1165/ajrcmb.19.1.2953. PMID 9651190.
  7. ^ a b "Entrez Gene: PDPN podoplanin".
  8. ^ a b c d Astarita JL, Acton SE, Turley SJ (2012). "Podoplanin: emerging functions in development, the immune system, and cancer". Frontiers in Immunology. 3: 283. doi:10.3389/fimmu.2012.00283. PMC 3439854. PMID 22988448.
  9. ^ a b Fu J, Gerhardt H, McDaniel JM, Xia B, Liu X, Ivanciu L, Ny A, Hermans K, Silasi-Mansat R, McGee S, Nye E, Ju T, Ramirez MI, Carmeliet P, Cummings RD, Lupu F, Xia L (November 2008). "Endothelial cell O-glycan deficiency causes blood/lymphatic misconnections and consequent fatty liver disease in mice". The Journal of Clinical Investigation. 118 (11): 3725–37. doi:10.1172/JCI36077. PMC 2567837. PMID 18924607.
  10. ^ Imaizumi Y, Amano I, Tsuruga E, Kojima H, Sawa Y (October 2010). "Immunohistochemical examination for the distribution of podoplanin-expressing cells in developing mouse molar tooth germs". Acta Histochemica et Cytochemica. 43 (5): 115–21. doi:10.1267/ahc.10023. PMC 2965832. PMID 21060740.
  11. ^ Herzog BH, Fu J, Wilson SJ, Hess PR, Sen A, McDaniel JM, Pan Y, Sheng M, Yago T, Silasi-Mansat R, McGee S, May F, Nieswandt B, Morris AJ, Lupu F, Coughlin SR, McEver RP, Chen H, Kahn ML, Xia L (October 2013). "Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2". Nature. 502 (7469): 105–9. Bibcode:2013Natur.502..105H. doi:10.1038/nature12501. PMC 3791160. PMID 23995678.
  12. ^ Kitano H, Kageyama S, Hewitt SM, Hayashi R, Doki Y, Ozaki Y, Fujino S, Takikita M, Kubo H, Fukuoka J (October 2010). "Podoplanin expression in cancerous stroma induces lymphangiogenesis and predicts lymphatic spread and patient survival". Archives of Pathology & Laboratory Medicine. 134 (10): 1520–7. doi:10.5858/2009-0114-OA.1. PMC 7556323. PMID 20923309.
  13. ^ Chuang WY, Yeh CJ, Chao YK, Liu YH, Chang YS, Tseng CK, Chang HK, Wan YL, Hsueh C (2014). "Concordant podoplanin expression in cancer-associated fibroblasts and tumor cells is an adverse prognostic factor in esophageal squamous cell carcinoma". International Journal of Clinical and Experimental Pathology. 7 (8): 4847–56. PMC 4152045. PMID 25197355.
  14. ^ Martín-Villar E, Borda-d'Agua B, Carrasco-Ramirez P, Renart J, Parsons M, Quintanilla M, Jones GE (August 2015). "Podoplanin mediates ECM degradation by squamous carcinoma cells through control of invadopodia stability". Oncogene. 34 (34): 4531–44. doi:10.1038/onc.2014.388. PMC 4430312. PMID 25486435.

Further reading

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  • Overview of all the structural information available in the PDB for UniProt: Q86YL7 (Human Podoplanin) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: Q62011 (Mouse Podoplanin) at the PDBe-KB.