Biology:PODXL

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Podocalyxin-like protein 1 is a protein that in humans is encoded by the PODXL gene.[1]

Function

This gene encodes a member of the CD34 sialomucin protein family.[2] The encoded protein was originally identified as an important component of glomerular podocytes. Inactivation of the encoding gene in mice leads to anuria, omphalocele and perinatal death.[3] Podocytes are highly differentiated epithelial cells with interdigitating foot processes covering the outer aspect of the glomerular basement membrane. Other biological activities of the encoded protein include: binding in a membrane protein complex with Na+/H+ exchanger regulatory factor to intracellular cytoskeletal elements, playing a role in hematopoietic cell differentiation, and being expressed in vascular endothelium cells and binding to L-selectin.[1]

Expression

The expression and localisation of PODXL in human cells, tissues and organs have been investigated by the Human Protein Atlas consortium.[4] According to antibody-based profiling, the protein is present in glomerular podocytes, endothelial cells, glandular cells in fallopian tube, uterus and seminal vesicle and according to RNA expression analysis, the PODXL transcripts are present in all analysed human tissues.[5] Based on confocal microscopy,[6] the protein is mainly localised to the plasma membrane and microtubule organizing center and in addition localized to vesicles.[7]

Interactions

PODXL has been shown to interact with Sodium-hydrogen exchange regulatory cofactor 2.[8][9][10]

Clinical significance

Podocalyxin is upregulated in a number of cancers and is frequently associated with poor prognosis.[11] Based on patient survival data,[12] high level of PODXL transcripts in tumor cells is associated with poor prognosis in renal cancer.

References

  1. ↑ 1.0 1.1 "Entrez Gene: PODXL podocalyxin-like". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5420. 
  2. ↑ "Novel functions of the CD34 family". Journal of Cell Science 121 (Pt 22): 3683–92. November 2008. doi:10.1242/jcs.037507. PMID 18987355. 
  3. ↑ "Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin". The Journal of Experimental Medicine 194 (1): 13–27. July 2001. doi:10.1084/jem.194.1.13. PMID 11435469. 
  4. ↑ Uhlen et al (2015) Science 347: 1260419. https://doi.org/doi:10.1126/science.1260419
  5. ↑ "Tissue expression of PODXL - Summary - the Human Protein Atlas". http://www.proteinatlas.org/ENSG00000128567-PODXL/tissue. 
  6. ↑ Thul et al (2017) Science 356 (6340): eaal3321. https://doi.org/doi:10.1126/science.aal3321
  7. ↑ "Cell atlas - PODXL - the Human Protein Atlas". http://www.proteinatlas.org/ENSG00000128567-PODXL/cell. 
  8. ↑ "Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells". The Journal of Cell Biology 168 (2): 303–13. Jan 2005. doi:10.1083/jcb.200407072. PMID 15642748. 
  9. ↑ "Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton". The Journal of Clinical Investigation 108 (2): 289–301. Jul 2001. doi:10.1172/JCI12539. PMID 11457882. 
  10. ↑ "PDZ domain-mediated interaction of rabbit podocalyxin and Na(+)/H(+) exchange regulatory factor-2". American Journal of Physiology. Renal Physiology 282 (6): F1129–39. Jun 2002. doi:10.1152/ajprenal.00131.2001. PMID 11997330. 
  11. ↑ "Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy". Breast Cancer Research 17 (1): 46. March 2015. doi:10.1186/s13058-015-0562-7. PMID 25887862. 
  12. ↑ Uhlen et al (2017) Science 357 (6352): eaan2507. https://doi.org/doi:10.1126/science.aan2507

Further reading




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