STAT3 integrates cytokine and neurotrophin signals to promote sympathetic axon regeneration

Michael J. Pellegrino, Beth Habecker

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The transcription factor STAT3 has been implicated in axon regeneration. Here we investigate a role for STAT3 in sympathetic nerve sprouting after myocardial infarction (MI) - a common injury in humans. We show that NGF stimulates serine phosphorylation (S727) of STAT3 in sympathetic neurons via ERK1/2, in contrast to cytokine phosphorylation of Y705. Maximal sympathetic axon regeneration in vitro requires phosphorylation of both S727 and Y705. Furthermore, cytokine signaling is necessary for NGF-induced sympathetic nerve sprouting in the heart after MI. Transfection studies in neurons lacking STAT3 suggest two independent pools of STAT3, phosphorylated on either S727 or Y705, that regulate sympathetic regeneration via both transcriptional and non-transcriptional means. Additional data identify STAT3-microtubule interactions that may complement the well-characterized role of STAT3 stimulating regeneration associated genes. These data show that STAT3 is critical for sympathetic axon regeneration in vitro and in vivo, and identify a novel non-transcriptional mode of action.

Original languageEnglish (US)
Pages (from-to)272-282
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume56
DOIs
StatePublished - Sep 2013

Fingerprint

Nerve Growth Factors
Axons
Regeneration
Cytokines
Phosphorylation
Nerve Growth Factor
Myocardial Infarction
Neurons
STAT3 Transcription Factor
Microtubules
Serine
Transfection
Wounds and Injuries
Genes
In Vitro Techniques

Keywords

  • Ciliary neurotrophic factor
  • Myocardial infarction
  • Nerve growth factor
  • Signal transducer and activator of transcription 3
  • Sympathetic axon regeneration

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

STAT3 integrates cytokine and neurotrophin signals to promote sympathetic axon regeneration. / Pellegrino, Michael J.; Habecker, Beth.

In: Molecular and Cellular Neuroscience, Vol. 56, 09.2013, p. 272-282.

Research output: Contribution to journalArticle

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