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

H. L. Zhang, R. H. Singer, Gary J. Bassell

Research output: Contribution to journalArticle

158 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)59-70
Number of pages12
JournalJournal of Cell Biology
Volume147
Issue number1
DOIs
StatePublished - Oct 4 1999

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Keywords

  • Growth cone
  • Neurite outgrowth
  • Neurotrophin
  • mRNA localization
  • β-actin

ASJC Scopus subject areas

  • Cell Biology

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