RT Journal Article
SR Electronic
T1 Netrin-1-Induced Local β-Actin Synthesis and Growth Cone Guidance Requires Zipcode Binding Protein 1
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9800
OP 9813
DO 10.1523/JNEUROSCI.0166-11.2011
VO 31
IS 27
A1 Kristy Welshhans
A1 Gary J. Bassell
YR 2011
UL http://www.jneurosci.org/content/31/27/9800.abstract
AB Local β-actin synthesis in growth cones of developing axons plays an important role in growth cone steering; however, the mRNA binding proteins required for this process are unknown. Here we used Zbp1/Imp1−/− mice to test the hypothesis that zipcode binding protein 1 (ZBP1) is required for the regulation of β-actin mRNA transport and local translation underlying growth cone guidance. To address the biological function of ZBP1, we developed a novel in vitro turning assay with primary cortical neuron balls having axons >1 mm in length and demonstrate that growth cones of mammalian neurons exhibit protein synthesis-dependent attraction to either netrin-1 or brain-derived neurotrophic factor (BDNF). Interestingly, this attraction is lost in Zbp1-deficient neurons. Furthermore, BDNF-stimulated β-actin mRNA localization was attenuated in Zbp1-deficient neurons, which impaired enrichment of β-actin protein in the growth cone. Finally, using a photoconvertible translation reporter, we found that ZBP1 is necessary for netrin-1 stimulated local translation of β-actin mRNA in axonal growth cones. Together, these results suggest that netrin-1- and BDNF-induced growth cone attraction required ZBP1-mediated local translation of β-actin mRNA, and therefore ZBP1 regulates protein synthesis-dependent axon guidance. Thus, mRNA binding proteins regulating local translation can control spatiotemporal protein expression in response to guidance cues and directional cell motility.