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SUMOylation of Fragile X Mental Retardation Protein: A Critical Mechanism of FMRP-Mediated Neuronal Function

  • Mingzhu Tang
  • Liqun Lu
  • Feng Xie
  • Linxi Chen
Research Highlight

Recently, Khayachi et al. [1] showed that fragile X mental retardation protein (FMRP) is an active substrate of the small ubiquitin-like modifier (SUMO) pathway in neurons. FMRP SUMOylation is induced by the activation of metabotropic glutamate receptors (mGlu5Rs). FMRP SUMOylation is required for dissociating FMRP from dendritic RNA granules and controlling spine density and proper maturation. Mechanically, the SUMOylation process is triggered by the activation of mGlu5Rs, thereby contributing to maintaining FMRP-mediated neuronal function. In fact, some proteins that mediate synaptic plasticity, neurotransmitter release, and neuronal network formation [2, 3, 4], are mostly regulated by SUMOylation. Therefore, SUMOylation has emerged as an essential posttranslational modification in the nervous system. This novel discovery first provides evidence to support the idea that FMRP is a novel substrate of SUMOylation and acts as an essential regulator in the developing brain. Clearly, it...

Notes

Acknowledgements

This highlight was supported by the National Natural Science Foundation of China (81503074).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Khayachi A, Gwizdek C, Poupon G, Alcor D, Chafai M, Casse F, et al. Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation. Nat Commun 2018, 9: 757.CrossRefGoogle Scholar
  2. 2.
    Narayanan U, Nalavadi V, Nakamoto M, Pallas DC, Ceman S, Bassell GJ, et al. FMRP phosphorylation reveals an immediate-early signaling pathway triggered by group I mGluR and mediated by PP2A. J Neurosci 2007, 27: 14349–14357.CrossRefGoogle Scholar
  3. 3.
    Elrouby N. Analysis of small ubiquitin-like modifier (sumo) targets reflects the essential nature of protein SUMOylation and provides insight to elucidate the role of SUMO in plant development. Plant Physiol 2015, 169: 1006–1017.CrossRefGoogle Scholar
  4. 4.
    Rocca DL, Wilkinson KA, Henley JM. SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis. Sci Rep 2017, 7: 877.CrossRefGoogle Scholar
  5. 5.
    Girach F, Craig TJ, Rocca DL, Henley JM. RIM1alpha SUMOylation is required for fast synaptic vesicle exocytosis. Cell Rep 2013, 5: 1294–1301.CrossRefGoogle Scholar
  6. 6.
    Shalizi A, Bilimoria PM, Stegmuller J, Gaudilliere B, Yang Y, Shuai K, et al. PIASx is a MEF2 SUMO E3 ligase that promotes postsynaptic dendritic morphogenesis. J Neurosci 2007, 27: 10037–10046.CrossRefGoogle Scholar
  7. 7.
    Cheng J, Huang M, Zhu Y, Xin YJ, Zhao YK, Huang J, et al. SUMOylation of MeCP2 is essential for transcriptional repression and hippocampal synapse development. J Neurochem 2014, 128: 798–806.CrossRefGoogle Scholar
  8. 8.
    Usui N, Co M, Harper M, Rieger MA, Dougherty JD, Konopka G. Sumoylation of FOXP2 regulates motor function and vocal communication through Purkinje cell development. Biol Psychiatry 2017, 81: 220–230.CrossRefGoogle Scholar
  9. 9.
    Craig TJ, Anderson D, Evans AJ, Girach F, Henley JM. SUMOylation of Syntaxin1A regulates presynaptic endocytosis. Sci Rep 2015, 5: 17669.CrossRefGoogle Scholar
  10. 10.
    Liu F, Ni JJ, Sun FY. Expression of phospho-MeCP2s in the developing rat brain and function of postnatal MeCP2 in cerebellar neural cell development. Neurosci Bull 2017, 33: 1–16.CrossRefGoogle Scholar
  11. 11.
    Tai DJ, Liu YC, Hsu WL, Ma YL, Cheng SJ, Liu SY, et al. MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome. Nat Commun 2016, 7: 10552.CrossRefGoogle Scholar
  12. 12.
    Dorval V, Fraser PE. Small ubiquitin-like modifier (SUMO) modification of natively unfolded proteins tau and alpha-synuclein. J Biol Chem 2006, 281: 9919–9924.CrossRefGoogle Scholar
  13. 13.
    Hoppe JB, Rattray M, Tu H, Salbego CG, Cimarosti H. SUMO-1 conjugation blocks beta-amyloid-induced astrocyte reactivity. Neurosci Lett 2013, 546: 51–56.CrossRefGoogle Scholar
  14. 14.
    Myrick LK, Nakamoto-Kinoshita M, Lindor NM, Kirmani S, Cheng X, Warren ST. Fragile X syndrome due to a missense mutation. Eur J Hum Genet 2014, 22: 1185–1189.CrossRefGoogle Scholar
  15. 15.
    Bartley CM, O’Keefe RA, Blice-Baum A, Mihailescu MR, Gong X, Miyares L, et al. Mammalian FMRP S499 is phosphorylated by CK2 and promotes secondary phosphorylation of FMRP. eNeuro 2016, 3.Google Scholar
  16. 16.
    Berry-Kravis E, Hessl D, Coffey S, Hervey C, Schneider A, Yuhas J, et al. A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. J Med Genet 2009, 46: 266–271.CrossRefGoogle Scholar

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug StudyUniversity of South ChinaHengyangChina

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