PODXL explained

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.

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.

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Kershaw DB, Beck SG, Wharram BL, Wiggins JE, Goyal M, Thomas PE, Wiggins RC . Molecular cloning and characterization of human podocalyxin-like protein. Orthologous relationship to rabbit PCLP1 and rat podocalyxin . The Journal of Biological Chemistry . 272 . 25 . 15708–14 . Jun 1997 . 9188463 . 10.1074/jbc.272.25.15708 . free .
• Kershaw DB, Wiggins JE, Wharram BL, Wiggins RC . Assignment of the human podocalyxin-like protein (PODXL) gene to 7q32-q33 . Genomics . 45 . 1 . 239–40 . Oct 1997 . 9339384 . 10.1006/geno.1997.4934 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Sassetti C, Tangemann K, Singer MS, Kershaw DB, Rosen SD . Identification of podocalyxin-like protein as a high endothelial venule ligand for L-selectin: parallels to CD34 . The Journal of Experimental Medicine . 187 . 12 . 1965–75 . Jun 1998 . 9625756 . 2212365 . 10.1084/jem.187.12.1965 .
• Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags . Proceedings of the National Academy of Sciences of the United States of America . 97 . 7 . 3491–6 . Mar 2000 . 10737800 . 16267 . 10.1073/pnas.97.7.3491 . 2000PNAS...97.3491D . free .
• Takeda T, McQuistan T, Orlando RA, Farquhar MG . 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 . 11457882 . 203027 . 10.1172/JCI12539 .
• Li Y, Li J, Straight SW, Kershaw DB . 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 . 11997330 . 10.1152/ajprenal.00131.2001 .
• Schopperle WM, Kershaw DB, DeWolf WC . Human embryonal carcinoma tumor antigen, Gp200/GCTM-2, is podocalyxin . Biochemical and Biophysical Research Communications . 300 . 2 . 285–90 . Jan 2003 . 12504081 . 10.1016/S0006-291X(02)02844-9 .
• Koop K, Eikmans M, Baelde HJ, Kawachi H, De Heer E, Paul LC, Bruijn JA . Expression of podocyte-associated molecules in acquired human kidney diseases . Journal of the American Society of Nephrology . 14 . 8 . 2063–71 . Aug 2003 . 12874460 . 10.1097/01.ASN.0000078803.53165.C9 . free .
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation . Nature Biotechnology . 22 . 6 . 707–16 . Jun 2004 . 15146197 . 10.1038/nbt971 . 27764390 .
• Economou CG, Kitsiou PV, Tzinia AK, Panagopoulou E, Marinos E, Kershaw DB, Kerjaschki D, Tsilibary EC . Enhanced podocalyxin expression alters the structure of podocyte basal surface . Journal of Cell Science . 117 . Pt 15 . 3281–94 . Jul 2004 . 15226400 . 10.1242/jcs.01163 . 13492264 .
• 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 Research . 64 . 15 . 5068–73 . Aug 2004 . 15289306 . 10.1158/0008-5472.CAN-04-0240 . 1807.1/116 . 15399303 . free .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . Sep 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Meder D, Shevchenko A, Simons K, Füllekrug J . 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 . 15642748 . 2171597 . 10.1083/jcb.200407072 .
• Casey G, Neville PJ, Liu X, Plummer SJ, Cicek MS, Krumroy LM, Curran AP, McGreevy MR, Catalona WJ, Klein EA, Witte JS . Podocalyxin variants and risk of prostate cancer and tumor aggressiveness . Human Molecular Genetics . 15 . 5 . 735–41 . Mar 2006 . 16434482 . 10.1093/hmg/ddi487 . free .
• Butta N, Larrucea S, Alonso S, Rodriguez RB, Arias-Salgado EG, Ayuso MS, González-Manchón C, Parrilla R . Role of transcription factor Sp1 and CpG methylation on the regulation of the human podocalyxin gene promoter . BMC Molecular Biology . 7 . 17 . 2006 . 16684343 . 1481587 . 10.1186/1471-2199-7-17 . free .

Notes and References

1. Web site: Entrez Gene: PODXL podocalyxin-like.
2. Nielsen JS, McNagny KM . Novel functions of the CD34 family . Journal of Cell Science . 121 . Pt 22 . 3683–92 . November 2008 . 18987355 . 10.1242/jcs.037507 . 18154561 .
3. 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 . The Journal of Experimental Medicine . 194 . 1 . 13–27 . July 2001 . 11435469 . 2193439 . 10.1084/jem.194.1.13 .
4. Uhlen et al (2015) Science 347: 1260419. https://doi.org/doi:10.1126/science.1260419
5. Web site: Tissue expression of PODXL - Summary - the Human Protein Atlas.
6. Thul et al (2017) Science 356 (6340): eaal3321. https://doi.org/doi:10.1126/science.aal3321
7. Web site: Cell atlas - PODXL - the Human Protein Atlas.
8. Meder D, Shevchenko A, Simons K, Füllekrug J . 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 . 15642748 . 2171597 . 10.1083/jcb.200407072 .
9. Takeda T, McQuistan T, Orlando RA, Farquhar MG . 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 . 11457882 . 203027 . 10.1172/JCI12539 .
10. Li Y, Li J, Straight SW, Kershaw DB . 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 . 11997330 . 10.1152/ajprenal.00131.2001 .
11. Snyder KA, Hughes MR, Hedberg B, Brandon J, Hernaez DC, Bergqvist P, Cruz F, Po K, Graves ML, Turvey ME, Nielsen JS, Wilkins JA, McColl SR, Babcook JS, Roskelley CD, McNagny KM . Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy . Breast Cancer Research . 17 . 1 . 46 . March 2015 . 25887862 . 10.1186/s13058-015-0562-7 . 4423095 . free .
12. Uhlen et al (2017) Science 357 (6352): eaan2507. https://doi.org/doi:10.1126/science.aan2507