About this Journal Submit a Manuscript Table of Contents
Journal of Signal Transduction
Volume 2011 (2011), Article ID 563128, 11 pages
http://dx.doi.org/10.1155/2011/563128
Review Article

Podocyte Injury Associated with Mutant α-Actinin-4

1Department of Medicine, McGill University Health Centre, McGill University, Montreal, QC, Canada H3A 1A1
2Division of Nephrology, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, QC, Canada H3A 1A1
3Kidney Research Centre, Department of Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada K1H 8M5
4Departments of Medicine and CMM, Ottawa Hospital Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5

Received 14 March 2011; Accepted 8 May 2011

Academic Editor: Céline M. DerMardirossian

Copyright © 2011 Andrey V. Cybulsky and Chris R. J. Kennedy. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. Mundel and S. J. Shankland, “Podocyte biology and response to injury,” Journal of the American Society of Nephrology, vol. 13, no. 12, pp. 3005–3015, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. H. Pavenstädt, W. Kriz, and M. Kretzler, “Cell biology of the glomerular podocyte,” Physiological Reviews, vol. 83, no. 1, pp. 253–307, 2003. View at Scopus
  3. S. J. Shankland, “The podocyte's response to injury: role in proteinuria and glomerulosclerosis,” Kidney International, vol. 69, no. 12, pp. 2131–2147, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. K. Tryggvason, J. Patrakka, and J. Wartiovaara, “Hereditary proteinuria syndromes and mechanisms of proteinuria,” New England Journal of Medicine, vol. 354, no. 13, pp. 1387–1401, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. C. K. Chiang and R. Inagi, “Glomerular diseases: genetic causes and future therapeutics,” Nature Reviews Nephrology, vol. 6, no. 9, pp. 539–554, 2010. View at Publisher · View at Google Scholar
  6. B. L. Wharram, M. Goyal, J. E. Wiggins et al., “Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene,” Journal of the American Society of Nephrology, vol. 16, no. 10, pp. 2941–2952, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. R. C. Wiggins, “The spectrum of podocytopathies: a unifying view of glomerular diseases,” Kidney International, vol. 71, no. 12, pp. 1205–1214, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. T. Matsusaka, J. Xin, S. Niwa et al., “Genetic engineering of glomerular sclerosis in the mouse via control of onset and severity of podocyte-specific injury,” Journal of the American Society of Nephrology, vol. 16, no. 4, pp. 1013–1023, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. J. M. Kaplan, S. H. Kim, K. N. North et al., “Mutations in ACTN4, encoding α-actinin-4, cause familial focal segmental glomerulosclerosis,” Nature Genetics, vol. 24, no. 3, pp. 251–256, 2000. View at Publisher · View at Google Scholar · View at Scopus
  10. K. Honda, T. Yamada, R. Endo et al., “Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion,” Journal of Cell Biology, vol. 140, no. 6, pp. 1383–1393, 1998. View at Publisher · View at Google Scholar · View at Scopus
  11. A. H. Beggs, T. J. Byers, J. H. M. Knoll, F. M. Boyce, G. A. P. Bruns, and L. M. Kunkel, “Cloning and characterization of two human skeletal muscle α-actinin genes located on chromosomes 1 and 11,” Journal of Biological Chemistry, vol. 267, no. 13, pp. 9281–9288, 1992. View at Scopus
  12. C. A. Otey and O. Carpen, “α-actinin revisited: a fresh look at an old player,” Cell Motility and the Cytoskeleton, vol. 58, no. 2, pp. 104–111, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Ylanne, K. Scheffzek, P. Young, and M. Saraste, “Crystal structure of the α-actinin rod: four spectrin repeats forming a thight dimer,” Cellular and Molecular Biology Letters, vol. 6, p. 234, 2001.
  14. G. Franzot, B. Sjöblom, M. Gautel, and K. D. Carugo, “The crystal structure of the actin binding domain from α-actinin in its closed conformation: structural insight into phospholipid regulation of α-actinin,” Journal of Molecular Biology, vol. 348, no. 1, pp. 151–165, 2005. View at Publisher · View at Google Scholar
  15. K. Burridge and J. R. Feramisco, “Non-muscle α-actinins are calcium-sensitive actin-binding proteins,” Nature, vol. 294, no. 5841, pp. 565–567, 1981. View at Scopus
  16. K. Burridge and J. R. Feramisco, “α-actinin and vinculin from nonmuscle cells: calcium-sensitive interactions with actin,” Cold Spring Harbor Symposia on Quantitative Biology, vol. 46, pp. 587–597, 1982. View at Scopus
  17. T. S. Fraley, C. B. Pereira, T. C. Tran, C. Singleton, and J. A. Greenwood, “Phosphoinositide binding regulates α-actinin dynamics: mechanism for modulating cytoskeletal remodeling,” Journal of Biological Chemistry, vol. 280, no. 15, pp. 15479–15482, 2005. View at Publisher · View at Google Scholar
  18. T. S. Fraley, T. C. Tran, A. M. Corgan et al., “Phosphoinositide binding inhibits α-actinin bundling activity,” Journal of Biological Chemistry, vol. 278, no. 26, pp. 24039–24045, 2003. View at Publisher · View at Google Scholar
  19. J. L. R. Michaud, M. Hosseini-Abardeh, K. Farah, and C. R. J. Kennedy, “Modulating α-actinin-4 dynamics in podocytes,” Cell Motility and the Cytoskeleton, vol. 66, no. 3, pp. 166–178, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Izaguirre, L. Aguirre, P. Ji, B. Aneskievich, and B. Haimovich, “Tyrosine phosphorylation of α-actinin in activated platelets,” Journal of Biological Chemistry, vol. 274, no. 52, pp. 37012–37020, 1999. View at Publisher · View at Google Scholar · View at Scopus
  21. G. Izaguirre, L. Aguirre, Y. P. Hu et al., “The cytoskeletal/non-muscle isoform of α-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase,” Journal of Biological Chemistry, vol. 276, no. 31, pp. 28676–28685, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. W. T. Chen and S. J. Singer, “Immunoelectron microscopic studies of the sites of cell-substratum and cell-cell contacts in cultured fibroblasts,” Journal of Cell Biology, vol. 95, no. 1, pp. 205–222, 1982. View at Scopus
  23. G. Langanger, J. De Mey, and M. Moeremans, “Ultrastructural localization of α-actinin and filamin in cultured cells with the immunogold staining (IGS) method,” Journal of Cell Biology, vol. 99, no. 4 I, pp. 1324–1334, 1984.
  24. E. Lazarides and K. Burridge, “α-actinin: immunofluorescent localization of a muscle structural protein in nonmuscle cells,” Cell, vol. 6, no. 3, pp. 289–298, 1975. View at Scopus
  25. J. B. Meigs and Y. L. Wang, “Reorganization of α-actinin and vinculin induced by a phorbol ester in living cells,” Journal of Cell Biology, vol. 102, no. 4, pp. 1430–1438, 1986. View at Scopus
  26. K. M. Patrie, A. J. Drescher, A. Welihinda, P. Mundel, and B. Margolis, “Interaction of two actin-binding proteins, synaptopodin and α-actinin-4, with the tight junction protein MAGI-1,” Journal of Biological Chemistry, vol. 277, no. 33, pp. 30183–30190, 2002. View at Scopus
  27. S. Chakraborty, E. L. Reineke, M. Lam et al., “α-actinin 4 potentiates myocyte enhancer factor-2 transcription activity by antagonizing histone deacetylase 7,” Journal of Biological Chemistry, vol. 281, no. 46, pp. 35070–35080, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Khurana, S. Chakraborty, X. Cheng, Y.-T. Su, and H.-Y. Kao, “The actin-binding protein, actinin α 4 (ACTN4), is a nuclear receptor coactivator that promotes proliferation of MCF-7 breast cancer cells,” Journal of Biological Chemistry, vol. 286, no. 3, pp. 1850–1859, 2011. View at Publisher · View at Google Scholar
  29. V. N. Babakov, O. A. Petukhova, L. V. Turoverova et al., “RelA/NF-κB transcription factor associates with α-actinin-4,” Experimental Cell Research, vol. 314, no. 5, pp. 1030–1038, 2008. View at Publisher · View at Google Scholar
  30. J. Yao, T. C. Le, C. H. Kos et al., “α-actinin-4-mediated FSGS: an inherited kidney disease caused by an aggregated and rapidly degraded cytoskeletal protein,” PLoS Biology, vol. 2, no. 6, e167, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Ichimura, H. Kurihara, and T. Sakai, “Actin filament organization of foot processes in rat podocytes,” Journal of Histochemistry and Cytochemistry, vol. 51, no. 12, pp. 1589–1600, 2003. View at Scopus
  32. D. Drenckhahn and R. P. Franke, “Ultrastructural organization of contractile and cytoskeletal proteins in glomerular podocytes of chicken, rat, and man,” Laboratory Investigation, vol. 59, no. 5, pp. 673–682, 1988. View at Scopus
  33. J. L. R. Michaud, K. M. Chaisson, R. J. Parks, and C. R. J. Kennedy, “FSGS-associated α-actinin-4 (K256E) impairs cytoskeletal dynamics in podocytes,” Kidney International, vol. 70, no. 6, pp. 1054–1061, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. K. Bijian, T. Takano, J. Papillon et al., “Actin cytoskeleton regulates extracellular matrix-dependent survival signals in glomerular epithelial cells,” American Journal of Physiology, vol. 289, no. 6, pp. F1313–F1323, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. A. V. Cybulsky, T. Takano, J. Papillon, K. Bijian, J. Guillemette, and C. R. J. Kennedy, “Glomerular epithelial cell injury associated with mutant α-actinin-4,” American Journal of Physiology, vol. 297, no. 4, pp. F987–F995, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. S. V. Dandapani, H. Sugimoto, B. D. Matthews et al., “α-actinin-4 is required for normal podocyte adhesion,” Journal of Biological Chemistry, vol. 282, no. 1, pp. 467–477, 2007. View at Publisher · View at Google Scholar
  37. C. H. Kos, T. C. Le, S. Sinha et al., “Mice deficient in α-actinin-4 have severe glomerular disease,” Journal of Clinical Investigation, vol. 111, no. 11, pp. 1683–1690, 2003.
  38. J. M. Henderson, S. Al-Waheeb, A. Weins, S. V. Dandapani, and M. R. Pollak, “Mice with altered α-actinin-4 expression have distinct morphologic patterns of glomerular disease,” Kidney International, vol. 73, no. 6, pp. 741–750, 2008. View at Publisher · View at Google Scholar
  39. J. L. Michaud, E. Stitt-Cavanaugh, N. Endlich et al., “Mice with podocyte-specific overexpression of wild type α-actinin-4 are healthy controls for K256E-α-actinin-4 mutant transgenic mice,” Transgenic Research, vol. 19, no. 2, pp. 285–289, 2010. View at Publisher · View at Google Scholar
  40. J. M. Henderson, M. P. Alexander, and M. R. Pollak, “Patients with ACTN4 mutations demonstrate distinctive features of glomerular injury,” Journal of the American Society of Nephrology, vol. 20, no. 5, pp. 961–968, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. J. L. Michaud, L. I. Lemieux, M. Dubé, B. C. Vanderhyden, S. J. Robertson, and C. R. J. Kennedy, “Focal and segmental glomerulosclerosis in mice with podocyte-specific expression of mutant α-actinin-4,” Journal of the American Society of Nephrology, vol. 14, no. 5, pp. 1200–1211, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. A. Weins, P. Kenlan, S. Herbert et al., “Mutational and biological analysis of α-actinin-4 in focal segmental glomerulosclerosis,” Journal of the American Society of Nephrology, vol. 16, no. 12, pp. 3694–3701, 2005. View at Publisher · View at Google Scholar
  43. A. Weins, J. S. Schlondorff, F. Nakamura et al., “Disease-associated mutant α-actinin-4 reveals a mechanism for regulating its F-actin-binding affinity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 41, pp. 16080–16085, 2007. View at Publisher · View at Google Scholar
  44. S. M. Volkmer Ward, A. Weins, M. R. Pollak, and D. A. Weitz, “Dynamic viscoelasticity of actin cross-linked with wild-type and disease-causing mutant α-actinin-4,” Biophysical Journal, vol. 95, no. 10, pp. 4915–4923, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Y. Sherman and A. L. Goldberg, “Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases,” Neuron, vol. 29, no. 1, pp. 15–32, 2001. View at Publisher · View at Google Scholar · View at Scopus
  46. N. P. Dantuma and K. Lindsten, “Stressing the ubiquitin-proteasome system,” Cardiovascular Research, vol. 85, no. 2, pp. 263–271, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. R. R. Kopito, “ER quality control: the cytoplasmic connection,” Cell, vol. 88, no. 4, pp. 427–430, 1997. View at Publisher · View at Google Scholar · View at Scopus
  48. J. L. Brodsky, “The protective and destructive roles played by molecular chaperones during ERAD (endoplasmic-reticulum-associated degradation),” Biochemical Journal, vol. 404, no. 3, pp. 353–363, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. R. J. Kaufman, D. Scheuner, M. Schröder et al., “The unfolded protein response in nutrient sensing and differentiation,” Nature Reviews Molecular Cell Biology, vol. 3, no. 6, pp. 411–421, 2002. View at Publisher · View at Google Scholar · View at Scopus
  50. D. Ron and P. Walter, “Signal integration in the endoplasmic reticulum unfolded protein response,” Nature Reviews Molecular Cell Biology, vol. 8, no. 7, pp. 519–529, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. H. Yoshida, “ER stress and diseases,” FEBS Journal, vol. 274, no. 3, pp. 630–658, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. A. V. Cybulsky, “Endoplasmic reticulum stressin proteinuric kidney disease,” Kidney International, vol. 77, no. 3, pp. 187–193, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. R. Inagi, “Endoplasmic reticulum stress as a progression factor for kidney injury,” Current Opinion in Pharmacology, vol. 10, no. 2, pp. 156–165, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. T. Yoneda, F. Urano, and D. Ron, “Transmission of proteotoxicity across cellular compartments,” Genes and Development, vol. 16, no. 11, pp. 1307–1313, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. N. F. Bence, R. M. Sampat, and R. R. Kopito, “Impairment of the ubiquitin-proteasome system by protein aggregation,” Science, vol. 292, no. 5521, pp. 1552–1555, 2001. View at Publisher · View at Google Scholar · View at Scopus
  56. H. Sakahira, P. Breuer, M. K. Hayer-Hartl, and F. U. Hartl, “Molecular chaperones as modulators of polyglutamine protein aggregation and toxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, supplement 4, pp. 16412–16418, 2002. View at Publisher · View at Google Scholar · View at Scopus
  57. H. Nishitoh, A. Matsuzawa, K. Tobiume et al., “ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats,” Genes and Development, vol. 16, no. 11, pp. 1345–1355, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. D. S. T. Ong and J. W. Kelly, “Chemical and/or biological therapeutic strategies to ameliorate protein misfolding diseases,” Current Opinion in Cell Biology, vol. 23, no. 2, pp. 231–238, 2011. View at Publisher · View at Google Scholar