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

Neuron. 2001 Aug 2;31(2):261-75. doi: 10.1016/s0896-6273(01)00357-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions
  • Actins / analysis
  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • Astrocytes
  • Avian Proteins
  • Base Sequence
  • Biological Transport / drug effects
  • Cells, Cultured
  • Chick Embryo
  • Coculture Techniques
  • Cytoplasmic Granules / chemistry
  • Fluorescent Antibody Technique
  • Gene Expression
  • In Situ Hybridization
  • Microscopy, Fluorescence
  • Microtubules / chemistry
  • Molecular Sequence Data
  • Neurons / chemistry
  • Neurons / ultrastructure*
  • Neurotrophin 3 / pharmacology*
  • Oligonucleotides, Antisense / pharmacology
  • Prosencephalon
  • RNA, Messenger / analysis
  • RNA-Binding Proteins / analysis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Recombinant Fusion Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Sequence Homology
  • Transfection

Substances

  • 3' Untranslated Regions
  • Actins
  • Avian Proteins
  • Neurotrophin 3
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • ZBP1 protein, Gallus gallus
  • messenger ribonucleoprotein