The Role of Deimination in Regenerative Reprogramming of Neurons

Di Ding, Mabel Enriquez-Algeciras, Anddre Osmar Valdivia, Juan Torres, Cameron Pole, John W. Thompson, Tsung han Chou, Miguel Perez-Pinzon, Vittorio Porciatti, Susan Udin, Eric Nestler, Sanjoy K. Bhattacharya

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Neurons from the adult central nervous system (CNS) demonstrate limited mRNA transport and localized protein synthesis versus developing neurons, correlating with lower regenerative capacity. We found that deimination (posttranslational conversion of protein-bound arginine into citrulline) undergoes upregulation during early neuronal development while declining to a low basal level in adults. This modification is associated with neuronal arborization from amphibians to mammals. The mRNA-binding proteins (ANP32a, REF), deiminated in neurons, have been implicated in local protein synthesis. Overexpression of the deiminating cytosolic enzyme peptidyl arginine deiminase 2 in nervous systems results in increased neuronal transport and neurite outgrowth. We further demonstrate that enriching deiminated proteins rescues transport deficiencies both in primary neurons and mouse optic nerve even in the presence of pharmacological transport blockers. We conclude that deimination promotes neuronal outgrowth via enhanced transport and local protein synthesis and represents a new avenue for neuronal regeneration in the adult CNS.

Original languageEnglish (US)
Pages (from-to)2618-2639
Number of pages22
JournalMolecular Neurobiology
Volume56
Issue number4
DOIs
StatePublished - Apr 1 2019

Keywords

  • Deimination
  • Development
  • PAD2
  • Regeneration

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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    Ding, D., Enriquez-Algeciras, M., Valdivia, A. O., Torres, J., Pole, C., Thompson, J. W., Chou, T. H., Perez-Pinzon, M., Porciatti, V., Udin, S., Nestler, E., & Bhattacharya, S. K. (2019). The Role of Deimination in Regenerative Reprogramming of Neurons. Molecular Neurobiology, 56(4), 2618-2639. https://doi.org/10.1007/s12035-018-1262-y