RT Journal Article
SR Electronic
T1 Phosphorylation of Zipcode Binding Protein 1 Is Required for Brain-Derived Neurotrophic Factor Signaling of Local β-Actin Synthesis and Growth Cone Turning
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9349
OP 9358
DO 10.1523/JNEUROSCI.0499-10.2010
VO 30
IS 28
A1 Yukio Sasaki
A1 Kristy Welshhans
A1 Zhexing Wen
A1 Jiaqi Yao
A1 Mei Xu
A1 Yoshio Goshima
A1 James Q. Zheng
A1 Gary J. Bassell
YR 2010
UL http://www.jneurosci.org/content/30/28/9349.abstract
AB The localization of specific mRNAs and their local translation in growth cones of developing axons has been shown to play an important mechanism to regulate growth cone turning responses to attractive or repulsive cues. However, the mechanism whereby local translation and growth cone turning may be controlled by specific mRNA-binding proteins is unknown. Here we demonstrate that brain-derived neurotrophic factor (BDNF) signals the Src-dependent phosphorylation of the β-actin mRNA zipcode binding protein 1 (ZBP1), which is necessary for β-actin synthesis and growth cone turning. We raised a phospho-specific ZBP1 antibody to Tyr396, which is a Src phosphorylation site, and immunofluorescence revealed BDNF-induced phosphorylation of ZBP1 within growth cones. The BDNF-induced increase in fluorescent signal of a green fluorescent protein translation reporter with the 3′ untranslated region of β-actin was attenuated with the Src family kinase-specific inhibitor PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine]. Furthermore, a nonphosphorylatable mutant, ZBP1 Y396F, suppressed the BDNF-induced and protein synthesis-dependent increase in β-actin localization in growth cones. Last, the ZBP1 Y396F mutant blocked BDNF-induced attractive growth cone turning. These results indicate that phosphorylation of ZBP1 at Tyr396 within growth cones has a critical role to regulate local protein synthesis and growth cone turning. Our findings provide new insight into how the regulated phosphorylation of mRNA-binding proteins influences local translation underlying growth cone motility and axon guidance.