Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility.
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.
Zhang
H L
HL
Department of Neuroscience, Rose F. Kennedy Center for Mental Retardation, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Eom
T
T
Oleynikov
Y
Y
Shenoy
S M
SM
Liebelt
D A
DA
Dictenberg
J B
JB
Singer
R H
RH
Bassell
G J
GJ
D020413:3' Untranslated Regions; D000199:Actins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes; D030161:Avian Proteins; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D018920:Coculture Techniques; D003594:Cytoplasmic Granules / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000737:chemistry; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure*; D020933:Neurotrophin 3 / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016548:Prosencephalon; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D017385:Sequence Homology; D014162:Transfection
D020413:3' Untranslated Regions; D000199:Actins; D030161:Avian Proteins; D020933:Neurotrophin 3; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; C498636:ZBP1 protein, Gallus gallus; C026452:messenger ribonucleoprotein