Article abstract
Nature Cell Biology 10, 149 - 159 (2008)
Published online: 13 January 2008 | doi:10.1038/ncb1677
There is an Erratum (March 2008) associated with this Article.
Intra-axonal translation and retrograde trafficking of CREB promotes neuronal survival
Llewellyn J. Cox1, Ulrich Hengst1, Nadya G. Gurskaya2, Konstantin A. Lukyanov2 & Samie R. Jaffrey1
Abstract
During development of the nervous system, axons and growth cones contain mRNAs such as 
-actin, cofilin and RhoA, which are locally translated in response to guidance cues. Intra-axonal translation of these mRNAs results in local morphological responses; however, other functions of intra-axonal mRNA translation remain unknown. Here, we show that axons of developing mammalian neurons contain mRNA encoding the cAMP-responsive element (CRE)-binding protein (CREB). CREB is translated within axons in response to nerve growth factor (NGF) and is retrogradely trafficked to the cell body. In neurons that are selectively deficient in axonal CREB transcripts, increases in nuclear pCREB, CRE-mediated transcription and neuronal survival elicited by axonal application of NGF are abolished, indicating a signalling function for axonally synthesized CREB. These studies identify a signalling role for axonally derived CREB, and indicate that signal-dependent synthesis and retrograde trafficking of transcription factors enables specific transcriptional responses to signalling events at distal axons.
- Department of Pharmacology, Weill Medical College, Cornell University, New York, NY 10021, USA.
- Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, Moscow 117997, Russia.
Correspondence to: Samie R. Jaffrey1 e-mail: srj2003@med.cornell.edu
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