Neurotrophin regulation of beta-actin mRNA and protein localization within growth cones.
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 beta-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 beta-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 beta-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 beta-actin mRNA. Localization of beta-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 beta-actin mRNA. These results suggest that NT-3 activates a cAMP-dependent signaling mechanism to promote the microtubule-dependent localization of beta-actin mRNA within growth cones.
Zhang
H L
HL
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Singer
R H
RH
Bassell
G J
GJ
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003078:Colchicine / Q000494:pharmacology; D003470:Culture Media; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D020439:Growth Cones / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3 / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000199:Actins; D003470:Culture Media; D020933:Neurotrophin 3; D020033:Protein Isoforms; D012333:RNA, Messenger; D015638:Cytochalasin D; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D003078:Colchicine