Neurotrophin-induced transport of a β-actin mRNP complex increases β-actin levels and stimulates growth cone motility

被引:316
作者
Zhang, HL
Eom, T
Oleynikov, Y
Shenoy, SM
Liebelt, DA
Dictenberg, JB
Singer, RH
Bassell, GJ
机构
[1] Yeshiva Univ Albert Einstein Coll Med, Rose F Kennedy Ctr Mental Retardat, Dept Neurosci, Bronx, NY 10461 USA
[2] Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA
关键词
D O I
10.1016/S0896-6273(01)00357-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 Zip-code 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 P-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.
引用
收藏
页码:261 / 275
页数:15
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