Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs

• Published in: The Journal of cell biology Vol. 178; no. 6; pp. 965 - 980
• Main Authors: Willis, Dianna E, van Niekerk, Erna A, Sasaki, Yukio, Mesngon, Mariano, Merianda, Tanuja T, Williams, Gervan G, Kendall, Marvin, Smith, Deanna S, Bassell, Gary J, Twiss, Jeffery L
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 10-09-2007; Rockefeller University Press
• Subjects: Actins - genetics; Actins - metabolism; Animals; Axons; Axons - metabolism; Cells; Cells, Cultured; Gene expression regulation; Glycoproteins; Green Fluorescent Proteins - genetics; Growth cones; In Situ Hybridization; Ligands; Messenger RNA; Myelin-Associated Glycoprotein - metabolism; Nerve Growth Factors - physiology; Nerve Regeneration; Neurons; Neurons - metabolism; Neuroscience; Perceptual localization; Protein synthesis; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Semaphorin-3A - metabolism; Signal Transduction; Studies; Untranslated regions
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200703209

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.