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Author Notes:

Correspondence to Jeffery L. Twiss: twiss@medsci.udel.edu

Dr. Leslie Krueger (Nemours Biomedical Research) provided technical assistance for design and interpretation of qPCR analyses. The eGFPNLS/myr construct was provided by Dr. Erin Schumann.

Dr. Yoshio Goshima provided recombinant Sema3A and the corresponding control protein.

Subjects:

Research Funding:

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.

D.E. Willis is supported by a Ruth Kirschstein National Research Service Award (grant NS047821).

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.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • CELL BIOLOGY
  • RETINAL GROWTH CONES
  • MYELIN-ASSOCIATED GLYCOPROTEIN
  • SYNAPTIC ACTIVATION CAUSES
  • PROTEIN-SYNTHESIS
  • AXONAL REGENERATION
  • INTRACELLULAR-LOCALIZATION
  • CHEMOTROPIC RESPONSES
  • CYTOPLASMIC DYNEIN
  • SENSORY NEURONS
  • TRANSLATION

Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs

Journal Title:

Journal of Cell Biology

Volume:

Volume 178, Number 6

Publisher:

, Pages 965-980

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Rockefeller University Press.

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