An NGF-TrkA-mediated retrograde signal to transcription factor CREB in sympathetic neurons

Antonella Riccio, Brian A. Pierchala, Christopher L. Ciarallo, David D. Ginty

Research output: Contribution to journalArticlepeer-review

Abstract

Nerve growth factor (NGF) is a neurotrophic factor secreted by cells that are the targets of innervation of sympathetic and some sensory neurons. However, the mechanism by which the NGF signal is propagated from the axon terminal to the cell body, which can be more than 1 meter away, to influence biochemical events critical for growth and survival of neurons has remained unclear. An NGF-mediated signal transmitted from the terminals and distal axons of cultured rat sympathetic neurons to their nuclei regulated phosphorylation of the transcription factor CREB (cyclic adenosine monophosphate response element-binding protein). Internalization of NGF and its receptor tyrosine kinase TrkA, and their transport to the cell body, were required for transmission of this signal. The tyrosine kinase activity of TrkA was required to maintain it in an autophosphorylated state upon its arrival n the cell body and for propagation of the signal to CREB within neuronal nuclei. Thus, an NGF-TrkA complex is a messenger that delivers the NGF signal from axon terminals to cell bodies of sympathetic neurons.

Original languageEnglish (US)
Pages (from-to)1097-1100
Number of pages4
JournalScience
Volume277
Issue number5329
DOIs
StatePublished - Aug 22 1997

ASJC Scopus subject areas

  • General

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