Podocalyxin

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Podocalyxin, a sialoglycoprotein, is thought to be the major constituent of the glycocalyx of podocytes in the glomerulus (Bowman's capsule).[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 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] 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.[5][8][9][10] Sialylated, O-glycosylated glycoforms of podocalyxin expressed by colon carcinoma cells possess L-selectin and E-selectin binding activity, and may be pivotal to the metastatic spread of colon carcinoma cells.[11][12][13] 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.[14]

See also[edit]

References[edit]

  1. ^ Omim - Podocalyxin-Like; Podxl
  2. ^ Nielsen JS, McNagny KM (2008). "Novel functions of the CD34 family". Journal of Cell Science. 121 (Pt 22): 3682–3692. doi:10.1242/jcs.037507. PMID 18987355. 
  3. ^ Gartner, LP; Hiatt, Strum (2007). Cell Biology and Histology. Lippincott Williams and Wilkins. ISBN 978-0-7817-8577-8. 
  4. ^ a b Doyonnas R, Kershaw DB, Duhme C, Merkens H, Chelliah S, Graf T, McNagny KM (2001). "Anuria, Omphalocele, and Perinatal Lethality in Mice Lacking the Cd34-Related Protein Podocalyxin". J Exp Med. 194 (1): 13–27. doi:10.1084/jem.194.1.13. PMC 2193439Freely accessible. PMID 11435469. 
  5. ^ a b Nielsen JS, McNagny KM (2009). "The role of podocalyxin in health and disease". J Am Soc Nephrol. 20 (10): 1669–76. doi:10.1681/ASN.2008070782. PMID 19578008. 
  6. ^ Strilić B1, Kucera T; et al. (2009). "The molecular basis of vascular lumen formation in the developing mouse aorta". Dev Cell. 17 (4): 505–15. doi:10.1016/j.devcel.2009.08.011. PMID 19853564. 
  7. ^ Debruin EJ, Hughes MR, et al. (2014). "Podocalyxin regulates murine lung vascular permeability by altering endothelial cell adhesion". PLOS ONE. 9 (10): e108881. doi:10.1371/journal.pone.0108881. PMC 4193771Freely accessible. PMID 25303643. 
  8. ^ Snyder K, Hughes MR, Hedberg B, Brandon J, Hernaez D, Bergqvist P, et al. (2015). "Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy". Breast Cancer Research. 17 (1): 46. doi:10.1186/s13058-015-0562-7. 
  9. ^ Kelly M. McNagny, Michael R. Hughes, Marcia L. Graves, Erin J. DeBruin, Kimberly Snyder, Jane Cipollone, Michelle Turvey, Poh C. Tan, Shaun McColl and Calvin D. Roskelley (2012). Podocalyxin in the Diagnosis and Treatment of Cancer, Advances in Cancer Management, Prof. Ravinder Mohan (Ed.), ISBN 978-953-307-870-0, InTech, doi:10.5772/24274
  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 (2004). "Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression". Cancer Res. 64 (15): 5068–73. doi:10.1158/0008-5472.CAN-04-0240. PMID 15289306. 
  11. ^ Thomas SN, Schnaar RL, Konstantopoulos K (Mar 2009). "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. doi:10.1152/ajpcell.00472.2008. PMC 2660269Freely accessible. PMID 19118161. 
  12. ^ Konstantopoulos K, Thomas SN (2009). "Cancer cells in transit: the vascular interactions of tumor cells". Annu Rev Biomed Eng. 11: 177–202. doi:10.1146/annurev-bioeng-061008-124949. PMID 19413512. 
  13. ^ Thomas SN, Tong Z, Stebe KJ, Konstantopoulos K (2009). "Identification, characterization and utilization of tumor cell selectin ligands in the design of colon cancer diagnostics". Biorheology. 46 (3): 207–25. doi:10.3233/BIR-2009-0534. PMID 19581728. 
  14. ^ Nielsen JS, Graves ML, Chelliah S, Vogl AW, Roskelley CD, McNagny KM (2007). "The CD34-related molecule podocalyxin is a potent inducer of microvillus formation". PLOS ONE. 2 (2): e237. doi:10.1371/journal.pone.0000237. PMC 1796660Freely accessible. PMID 17311105.