Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs

• Type of Material: Article
• Authors: Dianna E. Willis, Alfred I. duPont Hospital for Children; Erna A. van Niekerk, University of Delaware; Yukio Sasaki, Emory University; Mariano Mesngon, University of South Carolina; Tanuja T. Merianda, Alfred I. duPont Hospital for Children; Gervan G. Williams, Alfred I. duPont Hospital for Children; Marvin Kendall, Alfred I. duPont Hospital for Children; Deanna S. Smith, University of South Carolina; Gary Bassell, Emory University; Jeffery L. Twiss, Alfred I. duPont Hospital for Children
• Language: English
• Date: 2007-09-10
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © The Rockefeller University Press.
• Final Published Version (URL): http://dx.doi.org/10.1083/jcb.200703209
• Title of Journal or Parent Work: Journal of Cell Biology
• ISSN: 0021-9525
• Volume: 178
• Issue: 6
• Start Page: 965
• End Page: 980
• Grant/Funding Information: Centers of Biomedical Research Excellence funds from the National Center for Research Resources/NIH (grant RR020173) provided institutional support for core resources through the Center for Pediatric Research.; D.E. Willis is supported by a Ruth Kirschstein National Research Service Award (grant NS047821).; This work was supported by grants from the NIH (NS041696 and NS049041 to J.L. Twiss and HD46368 to G.J. Bassell), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and programmatic funding from the Nemours Foundation.
• Keywords: CELL BIOLOGY; PROTEIN-SYNTHESIS; CHEMOTROPIC RESPONSES; Science & Technology; CYTOPLASMIC DYNEIN; SYNAPTIC ACTIVATION CAUSES; RETINAL GROWTH CONES; Life Sciences & Biomedicine; AXONAL REGENERATION; TRANSLATION; SENSORY NEURONS; MYELIN-ASSOCIATED GLYCOPROTEIN; Cell Biology; INTRACELLULAR-LOCALIZATION
• Research Categories: Health Sciences, General; Biology, Molecular; Biology, Cell

Abstract

Subcellular regulation of protein synthesis requires the correct localization of messenger RNAs (mRNAs) within the cell. In this study, we investigate whether the axonal localization of neuronal mRNAs is regulated by extracellular stimuli. By profiling axonal levels of 50 mRNAs detected in regenerating adult sensory axons, we show that neurotrophins can increase and decrease levels of axonal mRNAs. Neurotrophins (nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3) regulate axonal mRNA levels and use distinct downstream signals to localize individual mRNAs. However, myelin-associated glycoprotein and semaphorin 3A regulate axonal levels of different mRNAs and elicit the opposite effect on axonal mRNA levels from those observed with neurotrophins. The axonal mRNAs accumulate at or are depleted from points of ligand stimulation along the axons. The translation product of a chimeric green fluorescent protein-β-actin mRNA showed similar accumulation or depletion adjacent to stimuli that increase or decrease axonal levels of endogenous β-actin mRNA. Thus, extracellular ligands can regulate protein generation within subcellular regions by specifically altering the localized levels of particular mRNAs.