RNA polymerase 1-driven transcription as a mediator of BDNF-induced neurite outgrowth

Cynthia Gomes, Scott C. Smith, Mark N. Youssef, Jing Juan Zheng, Theo Hagg, Michal Hetman

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Neurite outgrowth is essential for development of the nervous system. Neurotrophins including BDNF are among extracellular signals that regulate neurite outgrowth. The ERK1/2 pathway contributes to intracellular signaling networks transducing the pro-neuritic effects of BDNF. In the nucleolus, RNA polymerase-1 (Pol1)-mediated transcription regulates ribosomal biogenesis, enabling cellular protein synthesis and growth. Hence, we tested the possibility that Pol1 is an effector for pro-neuritic signals such as BDNF. We report that Pol1-mediated nucleolar transcription was increased by BDNF in an ERK1/2-dependent manner in rat forebrain neurons. Conversely, in cultured hippocampal neurons, knockdown of a Pol1 coactivator, transcription initiation factor 1A (TIF1A), attenuated BDNF- or ERK1/2-induced neurite outgrowth. Also, upon overexpression, a constitutively active mutant of TIF1A strongly promoted neurite outgrowth, including increases in total neurite length and branching. Finally, overexpression of wild-type TIF1A enhanced the pro-neuritic effects of ERK1/2 activation. These observations indicate that the Pol1-mediated nucleolar transcription regulates neurite outgrowth and serves as a major pro-neuritic effector of the BDNF-activated ERK1/2 pathway. Thus, development of the nervous system appears critically dependent on the nucleolus.

Original languageEnglish (US)
Pages (from-to)4357-4363
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number6
DOIs
StatePublished - Feb 11 2011

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Brain-Derived Neurotrophic Factor
DNA-Directed RNA Polymerases
Transcription
Peptide Initiation Factors
Transcription Factors
MAP Kinase Signaling System
Neurology
Nervous System
Neurons
Nerve Growth Factors
Neurites
Prosencephalon
Neuronal Outgrowth
Rats
Chemical activation
Growth
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

RNA polymerase 1-driven transcription as a mediator of BDNF-induced neurite outgrowth. / Gomes, Cynthia; Smith, Scott C.; Youssef, Mark N.; Zheng, Jing Juan; Hagg, Theo; Hetman, Michal.

In: Journal of Biological Chemistry, Vol. 286, No. 6, 11.02.2011, p. 4357-4363.

Research output: Contribution to journalArticle

Gomes, Cynthia ; Smith, Scott C. ; Youssef, Mark N. ; Zheng, Jing Juan ; Hagg, Theo ; Hetman, Michal. / RNA polymerase 1-driven transcription as a mediator of BDNF-induced neurite outgrowth. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 6. pp. 4357-4363.
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