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Niceforo A, Marioli C, Colasuonno F, et al. Altered cytoskeletal arrangement in induced pluripotent stem cells (iPSCs) and motor neurons from patients with riboflavin transporter deficiency. Dis Model Mech. 2021;doi: 10.1242/dmm.046391.
Niceforo, A., Marioli, C., Colasuonno, F., Petrini, S., Massey, K., Tartaglia, M., Bertini, E., Moreno, S., & Compagnucci, C. (2021). Altered cytoskeletal arrangement in induced pluripotent stem cells (iPSCs) and motor neurons from patients with riboflavin transporter deficiency. Disease models & mechanisms, . https://doi.org/10.1242/dmm.046391
Niceforo, Alessia, et al. "Altered cytoskeletal arrangement in induced pluripotent stem cells (iPSCs) and motor neurons from patients with riboflavin transporter deficiency." Disease models & mechanisms vol. (2021). doi: https://doi.org/10.1242/dmm.046391
Niceforo A, Marioli C, Colasuonno F, Petrini S, Massey K, Tartaglia M, Bertini E, Moreno S, Compagnucci C. Altered cytoskeletal arrangement in induced pluripotent stem cells (iPSCs) and motor neurons from patients with riboflavin transporter deficiency. Dis Model Mech. 2021 Jan 19; doi: 10.1242/dmm.046391. Epub 2021 Jan 19. PMID: 33468503; PMCID: PMC7927654.
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Dis Model Mech. 2021 Jan 19; doi: 10.1242/dmm.046391. Epub 2021 Jan 19.

Altered cytoskeletal arrangement in induced pluripotent stem cells (iPSCs) and motor neurons from patients with riboflavin transporter deficiency.

Disease models & mechanisms

Alessia Niceforo, Chiara Marioli, Fiorella Colasuonno, Stefania Petrini, Keith Massey, Marco Tartaglia, Enrico Bertini, Sandra Moreno, Claudia Compagnucci

Affiliations

  1. Department of Science, LIME, University Roma Tre, Rome 00146, Italy.
  2. Department of Neuroscience, Unit of Neuromuscular and Neurodegenerative Diseases, Laboratory of Molecular Medicine, IRCCS Ospedale Pediatrico Bambino Gesù, Rome 00146, Italy.
  3. Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Gesù, Rome 00146, Italy.
  4. Confocal Microscopy Core Facility, Research Laboratories, IRCCS Ospedale Pediatrico Bambino Gesù, Rome 00146, Italy.
  5. Science Director, Cure RTD Foundation, Canada.
  6. Genetics and Rare Diseases Research Division, IRCCS Ospedale Pediatrico Bambino Gesù, Rome 00146, Italy [email protected].

PMID: 33468503 PMCID: PMC7927654 DOI: 10.1242/dmm.046391

Abstract

The cytoskeletal network plays a crucial role in differentiation, morphogenesis, function and homeostasis of the nervous tissue, so that alterations in any of its components may lead to neurodegenerative diseases. Riboflavin transporter deficiency (RTD), a childhood-onset disorder characterized by degeneration of motor neurons (MNs), is caused by biallelic mutations in genes encoding the human riboflavin (RF) transporters. In a patient- specific induced Pluripotent Stem Cells (iPSCs) model of RTD, we recently demonstrated altered cell-cell contacts, energy dysmetabolism and redox imbalance.The present study focusses on cytoskeletal composition and dynamics associated to RTD, utilizing patients' iPSCs and derived MNs. Abnormal expression and distribution of α- and β-tubulin (α- and β-TUB), as well as imbalanced tyrosination of α-TUB, accompanied by impaired ability to repolymerize after nocodazole treatment, were found in RTD patient-derived iPSCs. Following differentiation, MNs showed consistent changes in TUB content, which was associated with abnormal morphofunctional features, such as neurite length and Ca

© 2021. Published by The Company of Biologists Ltd.

Keywords: IPSCs; Motor neurons; NAC; Riboflavin; Riboflavin transporter deficiency; Tubulin

References

  1. Arch Neurol. 1981 Mar;38(3):186-90 - PubMed
  2. J Inherit Metab Dis. 2019 Jul;42(4):598-607 - PubMed
  3. Top Magn Reson Imaging. 2018 Dec;27(6):395-408 - PubMed
  4. Neurochem Res. 1991 Feb;16(2):157-61 - PubMed
  5. Biochim Biophys Acta. 2016 May;1863(5):1019-26 - PubMed
  6. Front Cell Neurosci. 2015 Sep 30;9:381 - PubMed
  7. Oxid Med Cell Longev. 2020 Aug 12;2020:6821247 - PubMed
  8. Cell Mol Life Sci. 2014 May;71(9):1623-39 - PubMed
  9. Exp Cell Res. 2012 Aug 1;318(13):1528-41 - PubMed
  10. Regen Ther. 2017 Feb 10;6:41-51 - PubMed
  11. PLoS One. 2012;7(12):e48677 - PubMed
  12. Contemp Clin Trials. 2020 Apr;91:105961 - PubMed
  13. Ann Neurol. 1997 Aug;42(2):200-7 - PubMed
  14. Proc Natl Acad Sci U S A. 1970 Aug;66(4):1206-12 - PubMed
  15. Methods Mol Biol. 2016;1341:245-55 - PubMed
  16. Hum Mol Genet. 2016 May 1;25(9):1814-23 - PubMed
  17. Tissue Barriers. 2018;6(3):1539596 - PubMed
  18. Am J Hum Genet. 2010 Mar 12;86(3):485-9 - PubMed
  19. PLoS One. 2013;8(1):e54271 - PubMed
  20. Nature. 2012 Jan 18;481(7381):295-305 - PubMed
  21. Orphanet J Rare Dis. 2012 Oct 29;7:83 - PubMed
  22. Cell Mol Life Sci. 2018 Jan;75(2):163-176 - PubMed
  23. Hum Mol Genet. 2019 Sep 1;28(17):2835-2850 - PubMed
  24. Cell Commun Adhes. 2001;8(4-6):219-23 - PubMed
  25. Cell. 2006 Aug 25;126(4):663-76 - PubMed
  26. Sci Rep. 2014 Nov 11;4:6996 - PubMed
  27. J Med Genet. 2013 Feb;50(2):104-7 - PubMed
  28. Hum Mol Genet. 2016 Oct 1;25(19):4288-4301 - PubMed
  29. J Cell Sci. 2017 Apr 15;130(8):1347-1353 - PubMed
  30. Sci Rep. 2016 Jun 08;6:27557 - PubMed
  31. Br J Nutr. 2014 Jun 14;111(11):1985-91 - PubMed
  32. J Cell Biol. 1987 Jul;105(1):251-64 - PubMed
  33. Invest Ophthalmol Vis Sci. 2019 Dec 2;60(15):5104-5111 - PubMed
  34. Physiol Rev. 1989 Oct;69(4):1170-98 - PubMed
  35. Rev Neurol (Paris). 1966 Aug;115(2):289-95 - PubMed
  36. J Clin Med. 2017 May 05;6(5): - PubMed
  37. J Med Genet. 1990 Mar;27(3):176-9 - PubMed
  38. Science. 2017 Sep 1;357(6354):925-928 - PubMed
  39. Curr Biol. 2010 Jun 22;20(12):R528-37 - PubMed
  40. Neuroscience. 2011 Sep 29;192:285-94 - PubMed
  41. Biophys Chem. 2016 Apr;211:1-8 - PubMed
  42. J Neurol Sci. 1981 May;50(2):259-75 - PubMed
  43. Sci Rep. 2017 Apr 06;7:46271 - PubMed
  44. Brain. 2012 Sep;135(Pt 9):2875-82 - PubMed
  45. Cells. 2019 Oct 22;8(10): - PubMed
  46. Oncotarget. 2016 Apr 12;7(15):19414-29 - PubMed
  47. Brain Res Bull. 2016 Sep;126(Pt 3):217-225 - PubMed
  48. Neuron. 2012 Mar 8;73(5):862-85 - PubMed
  49. J Cell Biol. 2006 Sep 11;174(6):839-49 - PubMed
  50. Neuromuscul Disord. 2005 Aug;15(8):565-8 - PubMed
  51. J Cell Biol. 1989 Aug;109(2):663-73 - PubMed
  52. Cytoskeleton (Hoboken). 2016 Sep;73(9):442-60 - PubMed

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