Podocalyxin Explained

Symbol:PODXL
Podocalyxin
Pfam:PF06365
Interpro:IPR013836
Membranome Superfamily:136

Podocalyxin, a sialoglycoprotein, is thought to be the major constituent of the glycocalyx of podocytes in the glomerulus (Bowman's capsule) in the kidneys.[1] It is a member of the CD34 family of transmembrane sialomucins.[2] 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.[3] This function is further supported by knockout studies in mice which reveal an essential role in podocyte morphogenesis[4] [5] and a role in the opening of vascular lumens and regulation of vascular permeability.[6] [7] [8] Of note, this is the only cell surface sialomucin knockout known to display a lethal phenotype.[4]

Podocalyxin is also upregulated in a number of cancers and is frequently associated with poor prognosis.[9] [10] 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.[11] 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 cells possess L-selectin and E-selectin binding activity, and the affinity of the binding may be pivotal to the metastatic spread of colon carcinoma cells.[12] [13] [14] 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.[15]

Podocalyxin is also known as TRA-1-60 and is a marker of pluripotent stem cells.[16]

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.[17]

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

Notes and References

  1. https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602632 Omim - Podocalyxin-Like; Podxl
  2. Nielsen JS, McNagny KM . Novel functions of the CD34 family . Journal of Cell Science . 121. Pt 22 . 3682–3692 . 2008 . 18987355 . 10.1242/jcs.037507.
  3. Book: Gartner, LP . Hiatt, Strum . Cell Biology and Histology . 2007 . Lippincott Williams and Wilkins . 978-0-7817-8577-8 . registration .
  4. Doyonnas R, Kershaw DB, Duhme C, Merkens H, Chelliah S, Graf T, McNagny KM . Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin. J Exp Med. 194. 1 . 13–27 . 2001 . 11435469 . 2193439. 10.1084/jem.194.1.13.
  5. Nielsen JS, McNagny KM . The role of podocalyxin in health and disease. J Am Soc Nephrol. 20. 10 . 1669–76 . 2009 . 19578008 . 10.1681/ASN.2008070782. free.
  6. Cait . Jessica . Hughes . Michael R. . Zeglinski . Matthew R. . Chan . Allen W. . Osterhof . Sabrina . Scott . R. Wilder . Hernaez . Diana Canals . Cait . Alissa . Vogl . A. Wayne . Bernatchez . Pascal . Underhill . T. Michael . Granville . David J. . Murphy . Timothy H. . Roskelley . Calvin D. . McNagny . Kelly M. . Podocalyxin is required for maintaining blood–brain barrier function during acute inflammation . Proceedings of the National Academy of Sciences . 5 March 2019 . 116 . 10 . 4518–4527 . 10.1073/pnas.1814766116 . 30787191 . 6410846 . 2019PNAS..116.4518C . free .
  7. Strilić . Boris . Kučera . Tomáš . Eglinger . Jan . Hughes . Michael R. . McNagny . Kelly M. . Tsukita . Sachiko . Dejana . Elisabetta . Ferrara . Napoleone . Lammert . Eckhard . The Molecular Basis of Vascular Lumen Formation in the Developing Mouse Aorta . Developmental Cell . October 2009 . 17 . 4 . 505–515 . 10.1016/j.devcel.2009.08.011 . 19853564 . free .
  8. Debruin EJ, Hughes MR, etal . Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion . PLOS ONE . 9. 10 . e108881 . 2014 . 25303643 . 10.1371/journal.pone.0108881 . 4193771. 2014PLoSO...9j8881D . free .
  9. Snyder . Kimberly A . Hughes . Michael R . Hedberg . Bradley . Brandon . Jill . Hernaez . Diana Canals . Bergqvist . Peter . Cruz . Frederic . Po . Kelvin . Graves . Marcia L . Turvey . Michelle E . Nielsen . Julie S . Wilkins . John A . McColl . Shaun R . Babcook . John S . Roskelley . Calvin D . McNagny . Kelly M . Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy . Breast Cancer Research . 27 March 2015 . 17 . 1 . 46 . 10.1186/s13058-015-0562-7 . 25887862 . 4423095 . free .
  10. Somasiri A, Nielsen JS, Makretsov N, McCoy ML, Prentice L, Gilks CB, Chia SK, Gelmon KA, Kershaw DB, Huntsman DG, McNagny KM, Roskelley CD . Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression. Cancer Res. 64. 15 . 5068–73 . 2004 . 15289306 . 10.1158/0008-5472.CAN-04-0240. 1807.1/116 . 15399303. free .
  11. Web site: 2002 . UniProtKB - O00592 (PODXL_HUMAN) . May 1, 2022.
  12. Thomas SN, Schnaar RL, Konstantopoulos K . Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells . Am J Physiol Cell Physiol . 296 . 3 . C505–13. Mar 2009 . 19118161 . 2660269. 10.1152/ajpcell.00472.2008.
  13. Konstantopoulos K, Thomas SN . Cancer cells in transit: the vascular interactions of tumor cells. Annu Rev Biomed Eng . 11 . 177–202 . 2009 . 19413512 . 10.1146/annurev-bioeng-061008-124949. free .
  14. Thomas SN, Tong Z, Stebe KJ, Konstantopoulos K . Identification, characterization and utilization of tumor cell selectin ligands in the design of colon cancer diagnostics. Biorheology. 46 . 3 . 207–25 . 2009 . 19581728 . 10.3233/BIR-2009-0534.
  15. Nielsen JS, Graves ML, Chelliah S, Vogl AW, Roskelley CD, McNagny KM . The CD34-related molecule podocalyxin is a potent inducer of microvillus formation . PLOS ONE . 2. 2 . e237 . 2007 . 17311105 . 1796660 . 10.1371/journal.pone.0000237. 2007PLoSO...2..237N . free .
  16. Schopperle . WM . DeWolf . WC . The TRA-1-60 and TRA-1-81 human pluripotent stem cell markers are expressed on podocalyxin in embryonal carcinoma. . Stem Cells . March 2007 . 25 . 3 . 723–30 . 10.1634/stemcells.2005-0597 . 17124010. 25224638 . free .
  17. Web site: 2000 . UniProtKB - Q9NZ53 (PDXL2_HUMAN) .

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