Display options
Cite
Dias C, Nita E, Faktor J, et al. CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity. iScience. 2021;24(8):102878doi: 10.1016/j.isci.2021.102878.
Dias, C., Nita, E., Faktor, J., Tynan, A. C., Hernychova, L., Vojtesek, B., Nylandsted, J., Hupp, T. R., Kunath, T., & Ball, K. L. (2021). CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity. iScience, 24(8), 102878. https://doi.org/10.1016/j.isci.2021.102878
Dias, Catarina, et al. "CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity." iScience vol. 24,8 (2021): 102878. doi: https://doi.org/10.1016/j.isci.2021.102878
Dias C, Nita E, Faktor J, Tynan AC, Hernychova L, Vojtesek B, Nylandsted J, Hupp TR, Kunath T, Ball KL. CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity. iScience. 2021 Jul 17;24(8):102878. doi: 10.1016/j.isci.2021.102878. eCollection 2021 Aug 20. PMID: 34401662; PMCID: PMC8350547.
Copy Download .nbib Format: NLM
Share it on

iScience. 2021 Jul 17;24(8):102878. doi: 10.1016/j.isci.2021.102878. eCollection 2021 Aug 20.

CHIP-dependent regulation of the actin cytoskeleton is linked to neuronal cell membrane integrity.

iScience

Catarina Dias, Erisa Nita, Jakub Faktor, Ailish C Tynan, Lenka Hernychova, Borivoj Vojtesek, Jesper Nylandsted, Ted R Hupp, Tilo Kunath, Kathryn L Ball

Affiliations

  1. Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK.
  2. Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, Edinburgh EH16 4UU, UK.
  3. Research Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
  4. University of Gdansk, International Centre for Cancer Vaccine Science, 80-822 Gdansk, Poland.
  5. Membrane Integrity Group, Danish Cancer Society Research Center, Strandboulevarden 49, 2100, Copenhagen, Denmark.

PMID: 34401662 PMCID: PMC8350547 DOI: 10.1016/j.isci.2021.102878

Abstract

CHIP is an E3-ubiquitin ligase that contributes to healthy aging and has been characterized as neuroprotective. To elucidate dominant CHIP-dependent changes in protein steady-state levels in a patient-derived human neuronal model, CHIP function was ablated using gene-editing and an unbiased proteomic analysis conducted to compare knock-out and wild-type isogenic induced pluripotent stem cell (iPSC)-derived cortical neurons. Rather than a broad effect on protein homeostasis, loss of CHIP function impacted on a focused cohort of proteins from actin cytoskeleton signaling and membrane integrity networks. In support of the proteomics, CHIP knockout cells had enhanced sensitivity to induced membrane damage. We conclude that the major readout of CHIP function in cortical neurons derived from iPSC of a patient with elevate α-synuclein, Parkinson's disease and dementia, is the modulation of substrates involved in maintaining cellular "health". Thus, regulation of the actin cytoskeletal and membrane integrity likely contributes to the neuroprotective function(s) of CHIP.

© 2021 The Authors.

Keywords: bioinformatics; cell biology; omics; organizational aspects of cell biology; proteomics

Conflict of interest statement

The authors declare no conflict of interest.

References

  1. Mol Cell Proteomics. 2015 Nov;14(11):2973-87 - PubMed
  2. Exp Cell Res. 2008 Nov 1;314(18):3318-25 - PubMed
  3. Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450 - PubMed
  4. Nat Rev Neurosci. 2013 Jan;14(1):38-48 - PubMed
  5. Nat Biotechnol. 2009 Mar;27(3):275-80 - PubMed
  6. J Microsc. 2008 Sep;231(3):446-54 - PubMed
  7. Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2649-61 - PubMed
  8. Mol Biol Cell. 2016 Jul 15;27(14):2272-85 - PubMed
  9. Int J Biol Sci. 2020 Jan 14;16(4):719-729 - PubMed
  10. J Biol Chem. 2012 Apr 6;287(15):12159-71 - PubMed
  11. Dis Model Mech. 2020 Oct 12;13(10): - PubMed
  12. Hum Mol Genet. 2017 Sep 15;26(18):3466-3481 - PubMed
  13. Curr Top Membr. 2019;84:17-41 - PubMed
  14. Mol Neurodegener. 2017 Jan 24;12(1):10 - PubMed
  15. Front Physiol. 2013 Jul 18;4:188 - PubMed
  16. Genomics. 2003 Mar;81(3):279-91 - PubMed
  17. J Biol Chem. 2010 Jul 23;285(30):23420-32 - PubMed
  18. Nature. 2006 Mar 23;440(7083):551-5 - PubMed
  19. Nat Cell Biol. 2002 Dec;4(12):955-62 - PubMed
  20. Science. 2010 Aug 13;329(5993):805-10 - PubMed
  21. Philos Trans R Soc Lond B Biol Sci. 2018 May 26;373(1747): - PubMed
  22. Front Immunol. 2019 Feb 19;10:225 - PubMed
  23. Cell Death Differ. 2017 May;24(5):903-916 - PubMed
  24. BMC Bioinformatics. 2009 Feb 03;10:48 - PubMed
  25. Nat Protoc. 2009;4(1):44-57 - PubMed
  26. Nat Cell Biol. 2001 Jan;3(1):100-5 - PubMed
  27. J Clin Invest. 2007 Mar;117(3):648-58 - PubMed
  28. Cell Motil Cytoskeleton. 2009 Aug;66(8):635-49 - PubMed
  29. J Allergy Clin Immunol. 2013 Sep;132(3):648-655.e1 - PubMed
  30. Genome Biol. 2014;15(12):550 - PubMed
  31. PLoS Comput Biol. 2007 Mar 23;3(3):e39 - PubMed
  32. Biochem Pharmacol. 2011 Mar 15;81(6):703-12 - PubMed
  33. Mol Cell. 2005 Nov 23;20(4):525-38 - PubMed
  34. Neuron. 2017 Jul 5;95(1):33-50 - PubMed
  35. J Biol Chem. 2007 Aug 3;282(31):22267-77 - PubMed
  36. Nat Commun. 2014 May 08;5:3795 - PubMed
  37. Nat Cell Biol. 2001 Jan;3(1):93-6 - PubMed
  38. Chem Phys Lipids. 2021 Mar;235:105034 - PubMed
  39. Proteomics. 2016 Sep;16(17):2327-44 - PubMed
  40. J Biol Chem. 2019 Jun 21;294(25):9799-9812 - PubMed
  41. J Cell Biol. 1990 Aug;111(2):721-9 - PubMed
  42. Nat Commun. 2011 Aug 23;2:440 - PubMed
  43. Biophys J. 2007 Dec 15;93(12):4225-36 - PubMed
  44. Proteomics. 2015 Apr;15(7):1215-23 - PubMed
  45. Nat Cell Biol. 2009 Jan;11(1):56-64 - PubMed
  46. Annu Rev Biochem. 2012;81:231-59 - PubMed
  47. Bioinformatics. 2014 Feb 15;30(4):523-30 - PubMed
  48. FASEB J. 2006 Apr;20(6):741-3 - PubMed
  49. Int J Biochem Cell Biol. 2015 Jan;58:37-52 - PubMed
  50. Mol Cell Biol. 2003 Jul;23(14):4948-58 - PubMed
  51. Mol Cell Biol. 2008 Jun;28(12):4018-25 - PubMed
  52. PLoS One. 2011 Jan 20;6(1):e16398 - PubMed
  53. Structure. 2015 Mar 3;23(3):472-482 - PubMed
  54. J Biol Chem. 2002 Nov 29;277(48):45920-7 - PubMed
  55. Front Mol Neurosci. 2016 Oct 04;9:93 - PubMed
  56. Mol Neurodegener. 2013 Jul 08;8:23 - PubMed
  57. J Neurol Neurosurg Psychiatry. 1989 Feb;52(2):185-92 - PubMed
  58. Physiol Rev. 2015 Oct;95(4):1205-40 - PubMed
  59. Curr Biol. 2010 Jan 26;20(2):143-8 - PubMed
  60. Mol Biol Cell. 2013 Apr;24(8):1232-49 - PubMed
  61. Elife. 2013 Apr 16;2:e00459 - PubMed
  62. PLoS One. 2011;6(7):e21800 - PubMed
  63. Mol Cell Biol. 2013 Nov;33(22):4461-72 - PubMed
  64. Mol Cell. 2019 Feb 21;73(4):699-713.e6 - PubMed
  65. Klin Onkol. 2016 Fall;29 Suppl 4(Suppl 4):54-58 - PubMed
  66. Biochim Biophys Acta. 2014 Feb;1838(2):605-19 - PubMed
  67. Sci Rep. 2019 Apr 30;9(1):6726 - PubMed
  68. Cell Stress Chaperones. 2009 Sep;14(5):445-57 - PubMed
  69. Cell Mol Life Sci. 2015 Dec;72(24):4795-805 - PubMed
  70. J Proteome Res. 2009 Jan;8(1):362-73 - PubMed
  71. Sci Rep. 2017 Sep 19;7(1):11857 - PubMed
  72. Braz J Med Biol Res. 2019;52(9):e8551 - PubMed
  73. Curr Med Chem. 2020;27(22):3600-3610 - PubMed
  74. J Exp Med. 2011 Sep 26;208(10):2099-112 - PubMed
  75. Sci Data. 2014 Sep 16;1:140031 - PubMed
  76. FEBS Lett. 2017 Sep;591(17):2616-2635 - PubMed
  77. Cell Biosci. 2013 Feb 06;3(1):7 - PubMed
  78. Nucleic Acids Res. 2019 Jan 8;47(D1):D607-D613 - PubMed
  79. EMBO J. 2003 Oct 15;22(20):5446-58 - PubMed
  80. J Cell Biol. 1991 Jul;114(2):255-61 - PubMed
  81. Nucleic Acids Res. 2009 Jan;37(1):1-13 - PubMed
  82. Semin Cell Dev Biol. 2015 Sep;45:18-23 - PubMed
  83. Elife. 2017 Nov 01;6: - PubMed
  84. Commun Integr Biol. 2019 Oct 13;12(1):162-165 - PubMed
  85. Sci Adv. 2018 Jan 03;4(1):e1701393 - PubMed
  86. Annu Rev Cell Dev Biol. 2003;19:541-64 - PubMed
  87. Front Physiol. 2013 Dec 17;4:372 - PubMed
  88. Int Rev Immunol. 2017 Sep 3;36(5):300-312 - PubMed
  89. Hum Mol Genet. 2008 Dec 15;17(24):3942-52 - PubMed
  90. Nat Commun. 2011;2:270 - PubMed
  91. Neurol Clin. 2001 Aug;19(3):607-27, vi - PubMed
  92. Biochem J. 2013 Feb 1;449(3):707-17 - PubMed
  93. Cell Mol Life Sci. 2015 Jun;72(11):2075-89 - PubMed
  94. J Cell Biol. 2003 May 26;161(4):737-47 - PubMed
  95. Mol Cell Biol. 1999 Jun;19(6):4535-45 - PubMed
  96. Bioarchitecture. 2016 Jul 3;6(4):61-75 - PubMed
  97. J Cell Biol. 2015 May 11;209(3):329-37 - PubMed
  98. Nat Neurosci. 2012 Feb 05;15(3):477-86, S1 - PubMed
  99. Nat Methods. 2009 May;6(5):359-62 - PubMed
  100. J Neurosci. 2007 May 9;27(19):5115-26 - PubMed
  101. J Physiol Biochem. 2012 Dec;68(4):485-91 - PubMed
  102. J Biol Chem. 1999 Jul 2;274(27):18893-901 - PubMed
  103. Cell. 2017 Apr 20;169(3):470-482.e13 - PubMed
  104. Sci Rep. 2018 Jul 9;8(1):10309 - PubMed
  105. EMBO Rep. 2001 Dec;2(12):1133-8 - PubMed
  106. J Biol Chem. 2011 Jan 7;286(1):607-19 - PubMed
  107. Histol Histopathol. 2000 Apr;15(2):539-49 - PubMed
  108. J Biol Chem. 2006 Sep 8;281(36):26714-24 - PubMed
  109. J Mol Biol. 2016 Oct 9;428(20):4031-4047 - PubMed
  110. J Biol Chem. 2005 Jun 24;280(25):23727-34 - PubMed
  111. Nat Methods. 2012 Jul;9(7):671-5 - PubMed
  112. Eur J Cell Biol. 2011 Dec;90(12):1016-28 - PubMed
  113. Nat Protoc. 2012 Oct;7(10):1836-46 - PubMed
  114. Cell Struct Funct. 2000 Feb;25(1):33-9 - PubMed

Publication Types