Podocyte-associated Proteins FAT, Alpha-actinin-4 and Filtrin Are Expressed in Langerhans Islets of the Pancreas

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2006 Jul 15

PMID 16841182

Citations 8

Authors

Johanna Rinta-Valkama

Tuula Palmen

Markus Lassila

Harry Holthofer

Affiliations

Soon will be listed here.

Abstract

Nephrin is a crucial podocyte molecule in the kidney glomerular filtration barrier and it is also expressed in Langerhans islet beta cells of the pancreas. Recently, genetic mapping of proteinuric kidney disease genes and animal models have revealed further important molecules for the kidney filtration function including alpha-actinin-4, podocin, FAT, and NEPH1. This study was addressed to explore the pancreatic expression of the podocyte molecules podocin, FAT, alpha-actinin-4, NEPH1, NEPH2, filtrin/NEPH3, synaptopodin and CD2 associated protein (CD2AP). The mRNA and protein expressions were studied by RT-PCR and immunoblotting, and localization in the pancreas was investigated by immunofluorescence. Of the nephrin-associated podocyte proteins, filtrin/NEPH3, FAT, and alpha-actinin-4 were found to be expressed in the pancreas at the gene and protein level and localized to Langerhans islets. Immunoreactivity with the podocin antibody was detected mostly in the exocrine pancreas. NEPH1 and synaptopodin expression was detected only at the mRNA level. Further studies are needed to unravel the functional role of these podocyte-associated molecules in the pancreatic Langerhans islets.

Citing Articles

Mass Spectrometry-Based Comprehensive Analysis of Pancreatic Cyst Fluids.

Paziewska A, Polkowski M, Rubel T, Karczmarski J, Wiechowska-Kozlowska A, Dabrowska M Biomed Res Int. 2019; 2018:7169595.

PMID: 30627566 PMC: 6304507. DOI: 10.1155/2018/7169595.

A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes.

Grahammer F, Wigge C, Schell C, Kretz O, Patrakka J, Schneider S JCI Insight. 2016; 1(9).

PMID: 27430022 PMC: 4943462. DOI: 10.1172/jci.insight.86177.

Nephrin Contributes to Insulin Secretion and Affects Mammalian Target of Rapamycin Signaling Independently of Insulin Receptor.

Villarreal R, Mitrofanova A, Maiguel D, Morales X, Jeon J, Grahammer F J Am Soc Nephrol. 2015; 27(4):1029-41.

PMID: 26400569 PMC: 4814188. DOI: 10.1681/ASN.2015020210.

Kin of IRRE-like Protein 2 Is a Phosphorylated Glycoprotein That Regulates Basal Insulin Secretion.

Yesildag B, Bock T, Herrmanns K, Wollscheid B, Stoffel M J Biol Chem. 2015; 290(43):25891-906.

PMID: 26324709 PMC: 4646245. DOI: 10.1074/jbc.M115.684704.

Nephrin is expressed on the surface of insulin vesicles and facilitates glucose-stimulated insulin release.

Fornoni A, Jeon J, Varona Santos J, Cobianchi L, Jauregui A, Inverardi L Diabetes. 2009; 59(1):190-9.

PMID: 19833886 PMC: 2797921. DOI: 10.2337/db09-0655.

References

Benson D, Lipman D, Ostell J, Rapp B, Wheeler D . GenBank. Nucleic Acids Res. 1999; 28(1):15-8. PMC: 102453. DOI: 10.1093/nar/28.1.15. View

Sun C, Kilburn D, Lukashin A, Crowell T, Gardner H, Brundiers R . Kirrel2, a novel immunoglobulin superfamily gene expressed primarily in beta cells of the pancreatic islets. Genomics. 2003; 82(2):130-42. DOI: 10.1016/s0888-7543(03)00110-1. View

Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A . NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet. 2000; 24(4):349-54. DOI: 10.1038/74166. View

Schwarz K, Simons M, Reiser J, Saleem M, Faul C, Kriz W . Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. J Clin Invest. 2001; 108(11):1621-9. PMC: 200981. DOI: 10.1172/JCI12849. View

Donoviel D, Freed D, Vogel H, Potter D, Hawkins E, Barrish J . Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein with homology to NEPHRIN. Mol Cell Biol. 2001; 21(14):4829-36. PMC: 87176. DOI: 10.1128/MCB.21.14.4829-4836.2001. View

Kawachi H, Kurihara H, Topham P, Brown D, Shia M, ORIKASA M . Slit diaphragm-reactive nephritogenic MAb 5-1-6 alters expression of ZO-1 in rat podocytes. Am J Physiol. 1998; 273(6):F984-93. DOI: 10.1152/ajprenal.1997.273.6.F984. View

Huber T, Kottgen M, Schilling B, Walz G, Benzing T . Interaction with podocin facilitates nephrin signaling. J Biol Chem. 2001; 276(45):41543-6. DOI: 10.1074/jbc.C100452200. View

Kuusniemi A, Kestila M, Patrakka J, Lahdenkari A, Ruotsalainen V, Holmberg C . Tissue expression of nephrin in human and pig. Pediatr Res. 2004; 55(5):774-81. DOI: 10.1203/01.PDR.0000117842.10241.2C. View

Kaplan J, Kim S, North K, Rennke H, Correia L, Tong H . Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet. 2000; 24(3):251-6. DOI: 10.1038/73456. View

10.

Zanone M, Favaro E, Doublier S, Lozanoska-Ochser B, Deregibus M, Greening J . Expression of nephrin by human pancreatic islet endothelial cells. Diabetologia. 2005; 48(9):1789-97. DOI: 10.1007/s00125-005-1865-5. View

11.

Kerjaschki D, Farquhar M . Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats. J Exp Med. 1983; 157(2):667-86. PMC: 2186920. DOI: 10.1084/jem.157.2.667. View

12.

Kurihara H, Anderson J, Farquhar M . Diversity among tight junctions in rat kidney: glomerular slit diaphragms and endothelial junctions express only one isoform of the tight junction protein ZO-1. Proc Natl Acad Sci U S A. 1992; 89(15):7075-9. PMC: 49648. DOI: 10.1073/pnas.89.15.7075. View

13.

Kestila M, Lenkkeri U, Mannikko M, Lamerdin J, McCready P, Putaala H . Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome. Mol Cell. 1998; 1(4):575-82. DOI: 10.1016/s1097-2765(00)80057-x. View

14.

Kos C, Le T, Sinha S, Henderson J, Kim S, Sugimoto H . Mice deficient in alpha-actinin-4 have severe glomerular disease. J Clin Invest. 2003; 111(11):1683-90. PMC: 156110. DOI: 10.1172/JCI17988. View

15.

Inoue T, Yaoita E, Kurihara H, Shimizu F, Sakai T, Kobayashi T . FAT is a component of glomerular slit diaphragms. Kidney Int. 2001; 59(3):1003-12. DOI: 10.1046/j.1523-1755.2001.0590031003.x. View

16.

Tryggvason K . Unraveling the mechanisms of glomerular ultrafiltration: nephrin, a key component of the slit diaphragm. J Am Soc Nephrol. 1999; 10(11):2440-5. DOI: 10.1681/ASN.V10112440. View

17.

Shih N, Li J, COTRAN R, Mundel P, Miner J, Shaw A . CD2AP localizes to the slit diaphragm and binds to nephrin via a novel C-terminal domain. Am J Pathol. 2001; 159(6):2303-8. PMC: 1850607. DOI: 10.1016/S0002-9440(10)63080-5. View

18.

Reiser J, Kriz W, Kretzler M, Mundel P . The glomerular slit diaphragm is a modified adherens junction. J Am Soc Nephrol. 2000; 11(1):1-8. DOI: 10.1681/ASN.V1111. View

19.

Tryggvason K, Ruotsalainen V, WARTIOVAARA J . Discovery of the congenital nephrotic syndrome gene discloses the structure of the mysterious molecular sieve of the kidney. Int J Dev Biol. 1999; 43(5):445-51. View

20.

Collares-Buzato C, Carvalho C, Furtado A, Boschero A . Upregulation of the expression of tight and adherens junction-associated proteins during maturation of neonatal pancreatic islets in vitro. J Mol Histol. 2004; 35(8-9):811-22. DOI: 10.1007/s10735-004-1746-0. View