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Neurotrophin
regulation of actin-dependent changes in growth cone motility may depend
on the signaling of beta-actin mRNA transport. Formation of an RNP complex
between the beta-actin mRNA zipcode sequence and Zipcode Binding Protein
1 (ZBP1) was required for its localization to growth cones. Antisense
oligonucleotides to the zipcode inhibited formation of this RNP complex
in vitro and the neurotrophin-induced localization of beta-actin mRNA
and ZBP1 granules. Live cell imaging of neurons transfected with EGFP-ZBP1
revealed fast, bidirectional movements of granules in neurites that were
inhibited by antisense treatment, as visualized by FRAP analysis. NT-3
stimulation of beta-actin protein localization was dependent on the 3'UTR
and inhibited by antisense treatment. Growth cones exhibited impaired
motility in the presense of antisense. These results suggest a novel mechanism
to influence growth cone dynamics involving the regulated transport of
mRNA. |
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