TITLE

Intra-axonal translation and retrograde trafficking of CREB promotes neuronal survival

AUTHOR(S)
Cox, Llewellyn J.; Hengst, Ulrich; Gurskaya, Nadya G.; Lukyanov, Konstantin A.; Jaffrey, Samie R.
PUB. DATE
February 2008
SOURCE
Nature Cell Biology;Feb2008, Vol. 10 Issue 2, p149
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
During development of the nervous system, axons and growth cones contain mRNAs such as β-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.
ACCESSION #
28791744

 

Related Articles

  • NGF and proNGF Regulate Functionally Distinct mRNAs in PC12 Cells: An Early Gene Expression Profiling. D'Onofrio, Mara; Paoletti, Francesca; Arisi, Ivan; Brandi, Rossella; Malerba, Francesca; Fasulo, Luisa; Cattaneo, Antonino // PLoS ONE;2011, Vol. 6 Issue 6, p1 

    The biological activities of NGF and of its precursor proNGF are quite distinct, due to different receptor binding profiles, but little is known about how proNGF regulates gene expression. Whether proNGF is a purely pro-apoptotic molecule and/or simply a "less potent NGF" is still a matter of...

  • Human MicroRNA Targets. John, Bino; Enright, Anton J.; Alexei3Aravin; Tuschl, Thomas; Sander, Chris; Marks, Debora S. // PLoS Biology;Nov2004, Vol. 2 Issue 11, p1862 

    MicroRNAs (miRNAs) interact with target mRNAs at specific sites to induce cleavage of the message or inhibit translation. The specific function of most mammalian miRNAs is unknown. We have predicted target sites on the 3' untranslated regions of human gene transcripts for all currently known 218...

  • The major mRNA-associated protein YB-1 is a potent 5' cap-dependent mRNA stabilizer. Evdokimova, Valentina; Ruzanov, Peter; Imataka, Hiroaki; Raught, Brian; Svitkin, Yuri; Ovchinnikov, Lev P.; Sonenberg, Nahum // EMBO Journal;10/1/2001, Vol. 20 Issue 19, p5491 

    mRNA silencing and storage play an important role in gene expression under diverse circumstances, such as throughout early metazoan development and in response to many types of environmental stress. Here we demonstrate that the major mRNA-associated protein YB-1, also termed p50, is a potent...

  • Identification of proteins specifically interacting with YB-1 mRNA 3′ UTR and the effect of hnRNP Q on YB-1 mRNA translation. Lyabin, D.; Nigmatullina, L.; Doronin, A.; Eliseeva, I.; Ovchinnikov, L. // Biochemistry (00062979);Jun2013, Vol. 78 Issue 6, p651 

    In this study, proteins specifically interacting with the 3′ untranslated region (UTR) of mRNA of the multifunctional Y-box-binding protein 1 (YB-1) were identified. One of these, hnRNP Q, was shown to specifically interact with the regulatory element (RE) in YB-1 mRNA 3′ UTR and to...

  • Far upstream element binding protein 1: a commander of transcription, translation and beyond. Zhang, J; Chen, Q M // Oncogene;6/13/2013, Vol. 32 Issue 24, p2907 

    The far upstream binding protein 1 (FBP1) was first identified as a DNA-binding protein that regulates c-Myc gene transcription through binding to the far upstream element (FUSE) in the promoter region 1.5 kb upstream of the transcription start site. FBP1 collaborates with TFIIH and additional...

  • Poly (C)-Binding Protein 1 Regulates p63 Expression through mRNA Stability. Cho, Seong-Jun; Jung, Yong-Sam; Chen, Xinbin // PLoS ONE;Aug2013, Vol. 8 Issue 8, p1 

    p63, a transcription factor and p53 family protein, plays a crucial role in tumor suppression and development of various epithelial tissues. While p63 expression is controlled mostly by post-translational modifications, recent studies indicate that transcriptional and posttranscriptional...

  • RNA-Binding Proteins Impacting on Internal Initiation of Translation. Martínez-Salas, Encarnación; Lozano, Gloria; Fernandez-Chamorro, Javier; Francisco-Velilla, Rosario; Galan, Alfonso; Diaz, Rosa // International Journal of Molecular Sciences;Nov2013, Vol. 14 Issue 11, p21705 

    RNA-binding proteins (RBPs) are pivotal regulators of all the steps of gene expression. RBPs govern gene regulation at the post-transcriptional level by virtue of their capacity to assemble ribonucleoprotein complexes on certain RNA structural elements, both in normal cells and in response to...

  • Predicting transcription factor activities from combined analysis of microarray and ChIP data: a partial least squares approach. Boulesteix, Anne-Laure; Strimmer, Korbinian // Theoretical Biology & Medical Modelling;2005, Vol. 2, p23 

    Background: The study of the network between transcription factors and their targets is important for understanding the complex regulatory mechanisms in a cell. Unfortunately, with standard microarray experiments it is not possible to measure the transcription factor activities (TFAs) directly,...

  • Translational control of immune responses: from transcripts to translatomes. Piccirillo, Ciriaco A; Bjur, Eva; Topisirovic, Ivan; Sonenberg, Nahum; Larsson, Ola // Nature Immunology;Jun2014, Vol. 15 Issue 6, p503 

    Selective translational control of gene expression is emerging as a principal mechanism for the regulation of protein abundance that determines a variety of functions in both the adaptive immune system and the innate immune system. The translation-initiation factor eIF4E acts as a node for such...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics