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PMID: 11502257 Published · ppublish English Journal Article 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.

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

Neuron ·Vol. 31 ·No. 2 ·2001-08-02 ·Pages 261-75

Zhang HL, Eom T, Oleynikov Y, Shenoy SM, Liebelt DA, Dictenberg JB, Singer RH, Bassell GJ

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.

MeSH Terms
3' Untranslated Regions Actins/analysis,genetics,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,ultrastructure Neurotrophin 3/pharmacology Oligonucleotides, Antisense/pharmacology Prosencephalon RNA, Messenger/analysis RNA-Binding Proteins/analysis,genetics,metabolism Recombinant Fusion Proteins Reverse Transcriptase Polymerase Chain Reaction Ribonucleoproteins/genetics,metabolism Sequence Homology Transfection
Chemicals
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
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zhang H L
Department of Neuroscience, Rose F. Kennedy Center for Mental Retardation, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Eom T
Oleynikov Y
Shenoy S M
Liebelt D A
Dictenberg J B
Singer R H
Bassell G J
Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
DOI
10.1016/s0896-6273(01)00357-9
Published
2001-08-02
Pages
261-75
Language
English
Region
United States
NLM ID
8809320
Subset
IM
Grants
NIAMS NIH HHS · AR41480 · United States
NCI NIH HHS · CA09475-13 · United States
NIGMS NIH HHS · R01 GM55599 · United States
NINDS NIH HHS · R01 NS39641 · United States
NINDS NIH HHS · T32 NS07439 · United States
External Links
PubMed source DOI: 10.1016/s0896-6273(01)00357-9 View journal details
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