Neurotrophin Regulation of {beta}-Actin mRNA and Protein Localization within Growth Cones

doi:10.1083/jcb.147.1.59

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© The Rockefeller University Press, 0021-9525/1999/10/59/ $5.00
The Journal of Cell Biology, Volume 147, Number 1, October 4, 1999 59-70

Original Article

Neurotrophin Regulation of ß-Actin mRNA and Protein Localization within Growth Cones

H.L. Zhang^a, R.H. Singer^b, and G.J. Bassell^a
^a Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461
^b Department of Anatomy, Albert Einstein College of Medicine, Bronx, New York 10461

Correspondence to: G.J. Bassell, Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway, Bronx, NY 10461. Tel:(718) 430-3648 Fax:(718) 430-2960 E-mail:bassell{at}aecom.yu.edu.

Neurotrophins play an essential role in the regulation of actin-dependentchanges in growth cone shape and motility. We have studied whetherneurotrophin signaling can promote the localization of ß-actinmRNA and protein within growth cones. The regulated localizationof specific mRNAs within neuronal processes and growth conescould provide a mechanism to modulate cytoskeletal compositionand growth cone dynamics during neuronal development. We havepreviously shown that ß-actin mRNA is localized in granulesthat were distributed throughout processes and growth conesof cultured neurons. In this study, we demonstrate that thelocalization of ß-actin mRNA and protein to growth conesof forebrain neurons is stimulated by neurotrophin-3 (NT-3).A similar response was observed when neurons were exposed toforskolin or db-cAMP, suggesting an involvement of a cAMP signalingpathway. NT-3 treatment resulted in a rapid and transient stimulationof PKA activity that preceded the localization of ß-actinmRNA. Localization of ß-actin mRNA was blocked by priortreatment of cells with Rp-cAMP, an inhibitor of cAMP-dependentprotein kinase A. Depolymerization of microtubules, but notmicrofilaments, inhibited the NT-3–induced localizationof ß-actin mRNA. These results suggest that NT-3 activatesa cAMP-dependent signaling mechanism to promote the microtubule-dependentlocalization of ß-actin mRNA within growth cones.

Key Words: mRNA localization, ß-actin, neurotrophin, growth cone,neurite outgrowth

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