Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs

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 regenerat...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Abbreviations used in this paper: AV, adenovirus; BDNF, brain-derived neurotrophic factor; db-cAMP, dibutyral cAMP; DRB, 5,6-dichlorobenzimidazole riboside; DRG, dorsal root ganglion; eGFP, enhanced GFP; EHNA, erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride; GAP-43, 43-kD growth-associated protein; MAG, myelin-associated glycoprotein; NT3, neurotrophin-3; PI3K, phosphatidyl inositol-3 kinase; qPCR, quantitative PCR; Sema3A, semaphorin 3A; UTR, untranslated region. Correspondence to Jeffery L. Twiss: twiss@medsci.udel.edu
ISSN:	0021-9525 1540-8140
DOI:	10.1083/jcb.200703209