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Author Notes:

G.J. Bassell: bassell@aecom.yu.edu *At time of deposit: gary.bassell@emory.edu

We thank John Condeelis for helpful discussions and for providing rhodamine-actin for these experiments.

We thank Ken Kosik for helpful discussions. We thank Steve Braut for preparation of probes.

We thank Shailesh Shenoy and Maritza Martinez for assistance with digital imaging and figure preparation.

Subjects:

Research Funding:

This work was supported by the March of Dimes Foundation, National Science Foundation grant IBN9811384 and National Institutes of Health (NIH) grants RO1 GM55599 to G.J. Bassell and GM54887 and AR41480 to R.H. Singer.

H.L. Zhang is a Research Associate supported by a NIH training grant to M. Bennett (IT32 NS-07439-01).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • CELL BIOLOGY
  • mRNA localization
  • beta-actin
  • neurotrophin
  • growth cone
  • neurite outgrowth
  • MESSENGER-RNA LOCALIZATION
  • SIGNAL-TRANSDUCTION
  • SUBCELLULAR-LOCALIZATION
  • HIPPOCAMPAL-NEURONS
  • AXONAL-TRANSPORT
  • CULTURE
  • CELLS
  • OLIGODENDROCYTES
  • FILOPODIA
  • POLARITY

Neurotrophin regulation of beta-actin mRNA and protein localization within growth cones

Tools:

Journal Title:

Journal of Cell Biology

Volume:

Volume 147, Number 1

Publisher:

, Pages 59-70

Type of Work:

Article | Final Publisher PDF

Abstract:

Neurotrophins play an essential role in the regulation of actin- dependent changes in growth cone shape and motility. We have studied whether neurotrophin signaling can promote the localization of β-actin mRNA and protein within growth cones. The regulated localization of specific mRNAs within neuronal processes and growth cones could provide a mechanism to modulate cytoskeletal composition and growth cone dynamics during neuronal development. We have previously shown that β-actin mRNA is localized in granules that were distributed throughout processes and growth cones of cultured neurons. In this study, we demonstrate that the localization of β- actin mRNA and protein to growth cones of forebrain neurons is stimulated by neurotrophin-3 (NT-3). A similar response was observed when neurons were exposed to forskolin or db-cAMP, suggesting an involvement of a cAMP signaling pathway. NT-3 treatment resulted in a rapid and transient stimulation of PKA activity that preceded the localization of β-actin mRNA. Localization of β-actin mRNA was blocked by prior treatment of cells with Rp-cAMP, an inhibitor of cAMP-dependent protein kinase A. Depolymerization of microtubules, but not microfilaments, inhibited the NT-3-induced localization of β-actin mRNA. These results suggest that NT-3 activates a cAMP-dependent signaling mechanism to promote the microtubule-dependent localization of β- actin mRNA within growth cones.

Copyright information:

ã The Rockefeller University Press.

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