Display options
Cite
Lee GH, D'Arcangelo G. New Insights into Reelin-Mediated Signaling Pathways. Front Cell Neurosci. 2016;10:122doi: 10.3389/fncel.2016.00122.
Lee, G. H., & D'Arcangelo, G. (2016). New Insights into Reelin-Mediated Signaling Pathways. Frontiers in cellular neuroscience, 10122. https://doi.org/10.3389/fncel.2016.00122
Lee, Gum Hwa, and D'Arcangelo, Gabriella. "New Insights into Reelin-Mediated Signaling Pathways." Frontiers in cellular neuroscience vol. 10 (2016): 122. doi: https://doi.org/10.3389/fncel.2016.00122
Lee GH, D'Arcangelo G. New Insights into Reelin-Mediated Signaling Pathways. Front Cell Neurosci. 2016 May 09;10:122. doi: 10.3389/fncel.2016.00122. eCollection 2016. PMID: 27242434; PMCID: PMC4860420.
Copy Download .nbib Format: NLM
Share it on

Front Cell Neurosci. 2016 May 09;10:122. doi: 10.3389/fncel.2016.00122. eCollection 2016.

New Insights into Reelin-Mediated Signaling Pathways.

Frontiers in cellular neuroscience

Gum Hwa Lee, Gabriella D'Arcangelo

Affiliations

  1. College of Pharmacy, Chosun University Gwangju, South Korea.
  2. Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey Piscataway, NJ, USA.

PMID: 27242434 PMCID: PMC4860420 DOI: 10.3389/fncel.2016.00122

Abstract

Reelin, a multifunctional extracellular protein that is important for mammalian brain development and function, is secreted by different cell types in the prenatal or postnatal brain. The spatiotemporal regulation of Reelin expression and distribution during development relates to its multifaceted function in the brain. Prenatally Reelin controls neuronal radial migration and proper positioning in cortical layers, whereas postnatally Reelin promotes neuronal maturation, synaptic formation and plasticity. The molecular mechanisms underlying the distinct biological functions of Reelin during and after brain development involve unique and overlapping signaling pathways that are activated following Reelin binding to its cell surface receptors. Distinct Reelin ligand isoforms, such as the full-length protein or fragments generated by proteolytic cleavage differentially affect the activity of downstream signaling pathways. In this review, we discuss recent advances in our understanding of the signaling transduction pathways activated by Reelin that regulate different aspects of brain development and function. A core signaling machinery, including ApoER2/VLDLR receptors, Src/Fyn kinases, and the adaptor protein Dab1, participates in all known aspects of Reelin biology. However, distinct downstream mechanisms, such as the Crk/Rap1 pathway and cell adhesion molecules, play crucial roles in the control of neuronal migration, whereas the PI3K/Akt/mTOR pathway appears to be more important for dendrite and spine development. Finally, the NMDA receptor (NMDAR) and an unidentified receptor contribute to the activation of the MEK/Erk1/2 pathway leading to the upregulation of genes involved in synaptic plasticity and learning. This knowledge may provide new insight into neurodevelopmental or neurodegenerative disorders that are associated with Reelin dysfunction.

Keywords: brain development; dendrites; neuronal migration; signal transduction; synaptogenesis

References

  1. J Neurosci. 2009 Jun 10;29(23):7459-73 - PubMed
  2. Neuron. 2000 Jul;27(1):33-44 - PubMed
  3. J Biol Chem. 2002 Dec 20;277(51):49958-64 - PubMed
  4. PLoS One. 2013;8(1):e53635 - PubMed
  5. Neurosci Res. 1997 Nov;29(3):217-23 - PubMed
  6. J Neurosci. 2008 Dec 10;28(50):13551-62 - PubMed
  7. Brain Res Mol Brain Res. 2000 Jan 10;75(1):121-7 - PubMed
  8. Nat Commun. 2014 Mar 06;5:3443 - PubMed
  9. Curr Biol. 2003 Jan 8;13(1):18-26 - PubMed
  10. Nature. 1997 Oct 16;389(6652):730-3 - PubMed
  11. Genes Dev. 2007 Nov 1;21(21):2717-30 - PubMed
  12. J Neurosci. 2005 Sep 7;25(36):8209-16 - PubMed
  13. J Biol Chem. 2014 Jul 18;289(29):20307-17 - PubMed
  14. Am J Hum Genet. 2015 Jun 4;96(6):992-1000 - PubMed
  15. Neuron. 1997 Aug;19(2):239-49 - PubMed
  16. Nat Neurosci. 2011 Jun;14(6):697-703 - PubMed
  17. J Biol Chem. 2002 Oct 18;277(42):39944-52 - PubMed
  18. Neuron. 2013 Nov 20;80(4):934-46 - PubMed
  19. J Neurosci. 1997 Jan 1;17(1):23-31 - PubMed
  20. Nat Genet. 2000 Sep;26(1):93-6 - PubMed
  21. J Biol Chem. 2010 Feb 12;285(7):4896-908 - PubMed
  22. J Biol Chem. 2007 Jul 13;282(28):20544-52 - PubMed
  23. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15938-43 - PubMed
  24. Sci Signal. 2015 Jul 07;8(384):ra67 - PubMed
  25. Adv Anat Embryol Cell Biol. 1998;150:1-106 - PubMed
  26. Mol Cell Biol. 2007 Oct;27(20):7113-24 - PubMed
  27. J Biochem. 2016 Mar;159(3):305-12 - PubMed
  28. Mol Psychiatry. 2014 Apr;19(4):417-26 - PubMed
  29. Neuron. 2005 Aug 18;47(4):567-79 - PubMed
  30. J Neurosci. 1998 Oct 1;18(19):7779-99 - PubMed
  31. PLoS One. 2012;7(10):e46592 - PubMed
  32. Nat Genet. 2003 Nov;35(3):270-6 - PubMed
  33. Biochim Biophys Acta. 2015 May;1853(5):904-17 - PubMed
  34. J Biol Chem. 2003 Oct 3;278(40):38772-9 - PubMed
  35. Anat Embryol (Berl). 1983;168(1):73-86 - PubMed
  36. Mol Cell Biol. 1999 Jul;19(7):5179-88 - PubMed
  37. J Neurosci. 2005 Sep 14;25(37):8578-86 - PubMed
  38. EMBO J. 1997 Jan 2;16(1):121-32 - PubMed
  39. Genes Dev. 1999 Mar 15;13(6):643-8 - PubMed
  40. PLoS One. 2007 Feb 28;2(2):e252 - PubMed
  41. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3221-6 - PubMed
  42. J Neurosci. 2010 Mar 31;30(13):4636-49 - PubMed
  43. Cell Res. 2013 Apr;23(4):473-90 - PubMed
  44. Nature. 2014 Nov 13;515(7526):209-15 - PubMed
  45. Eur J Neurosci. 2013 May;37(9):1404-12 - PubMed
  46. Neuron. 1995 May;14(5):899-912 - PubMed
  47. Cell. 2014 Sep 11;158(6):1335-47 - PubMed
  48. J Biol Chem. 2010 Jun 25;285(26):19720-6 - PubMed
  49. J Neurosci. 2008 Oct 8;28(41):10339-48 - PubMed
  50. J Neurosci. 2015 Jul 29;35(30):10659-74 - PubMed
  51. Behav Neurosci. 2006 Aug;120(4):984-8 - PubMed
  52. Biochem J. 2004 Nov 15;384(Pt 1):1-8 - PubMed
  53. J Neurosci. 2011 Feb 16;31(7):2352-60 - PubMed
  54. Neuron. 2011 Feb 10;69(3):482-97 - PubMed
  55. J Neurosci. 2007 Apr 18;27(16):4243-52 - PubMed
  56. J Neurosci. 2007 Dec 12;27(50):13854-65 - PubMed
  57. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):9988-93 - PubMed
  58. J Neurosci. 1997 May 15;17(10):3599-609 - PubMed
  59. Nature. 1997 Jan 2;385(6611):70-4 - PubMed
  60. Neurosci Res. 2002 Aug;43(4):381-8 - PubMed
  61. Neurobiol Learn Mem. 2006 May;85(3):228-42 - PubMed
  62. Neuron. 2013 Aug 7;79(3):461-77 - PubMed
  63. Structure. 2010 Mar 10;18(3):320-31 - PubMed
  64. Brain Res Mol Brain Res. 1997 Oct 15;50(1-2):85-90 - PubMed
  65. Neuron. 2004 Apr 22;42(2):197-211 - PubMed
  66. Neurosci Lett. 2015 Jul 10;599:97-101 - PubMed
  67. J Comp Neurol. 2015 Feb 15;523(3):463-78 - PubMed
  68. Neuron. 2015 May 6;86(3):696-710 - PubMed
  69. Genes Dev. 2001 Mar 15;15(6):639-51 - PubMed
  70. Neuron. 2012 Oct 18;76(2):353-69 - PubMed
  71. J Neurosci. 2004 Jan 14;24(2):514-21 - PubMed
  72. Cereb Cortex. 2015 Oct;25(10):3640-53 - PubMed
  73. Curr Biol. 2000 Jul 27-Aug 10;10(15):877-85 - PubMed
  74. Cell. 2010 Nov 24;143(5):826-36 - PubMed
  75. Nature. 1995 Apr 20;374(6524):719-23 - PubMed
  76. Neuroscience. 2011 Aug 25;189:32-42 - PubMed
  77. Mol Interv. 2002 Feb;2(1):47-57 - PubMed
  78. J Biol Chem. 2014 May 2;289(18):12922-30 - PubMed
  79. Neuron. 1999 Oct;24(2):481-9 - PubMed
  80. Neuron. 1999 Oct;24(2):471-9 - PubMed
  81. PLoS One. 2012;7(10 ):e47793 - PubMed
  82. Psychopharmacology (Berl). 2006 Nov;189(1):95-104 - PubMed
  83. J Neurosci. 2013 Sep 25;33(39):15652-68 - PubMed
  84. J Neurosci. 2015 Mar 18;35(11):4776-87 - PubMed
  85. J Neurosci. 2007 Sep 19;27(38):10165-75 - PubMed
  86. Neuron. 2004 Jan 8;41(1):71-84 - PubMed
  87. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9729-34 - PubMed
  88. Brain Res. 2007 Oct 3;1172:1-9 - PubMed
  89. Mol Cell Biol. 2003 Dec;23(24):9293-302 - PubMed
  90. Front Cell Neurosci. 2015 Nov 26;9:447 - PubMed
  91. J Neurosci. 1999 Sep 1;19(17):7507-15 - PubMed
  92. Mol Cell Biol. 2004 Feb;24(3):1378-86 - PubMed
  93. Cell. 1999 Jun 11;97(6):689-701 - PubMed
  94. Mol Cell Biol. 2003 Oct;23(20):7210-21 - PubMed

Publication Types