Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1

Stefan Hüttelmaier, Daniel Zenklusen, Marcell Lederer, Jason Dictenberg, Mike Lorenz, XiuHua Meng, Gary J. Bassell, John S. Condeelis, Robert H. Singer

Research output: Contribution to journalArticle

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Abstract

Localization of Β-actin messenger RNA to sites of active actin polymerization modulates cell migration during embryogenesis, differentiation and possibly carcinogenesis. This localization requires the oncofetal protein ZBP1 (Zipcode binding protein 1), which binds to a conserved 54-nucleotide element in the 3′-untranslated region of the Β-actin mRNA known as the 'zipcode'. ZBP1 promotes translocation of the Β-actin transcript to actin-rich protrusions in primary fibroblasts and neurons. It is not known how the ZBP1-RNA complex achieves asymmetric protein sorting by localizing Β-actin mRNA. Here we show that chicken ZBP1 modulates the translation of Β-actin mRNA. ZBP1 associates with the Β-actin transcript in the nucleus and prevents premature translation in the cytoplasm by blocking translation initiation. Translation only occurs when the ZBP1-RNA complex reaches its destination at the periphery of the cell. At the endpoint of mRNA transport, the protein kinase Src promotes translation by phosphorylating a key tyrosine residue in ZBP1 that is required for binding to RNA. These sequential events provide both temporal and spatial control over Β-actin mRNA translation, which is important for cell migration and neurite outgrowth.

Original languageEnglish (US)
Pages (from-to)512-515
Number of pages4
JournalNature
Volume438
Issue number7067
DOIs
StatePublished - Nov 24 2005

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Actins
Carrier Proteins
Phosphorylation
Messenger RNA
RNA-Binding Proteins
Protein Biosynthesis
Cell Movement
3' Untranslated Regions
Protein Transport
Protein Binding
Polymerization
Protein Kinases
Embryonic Development
Tyrosine
Catalytic Domain
Carcinogenesis
Cytoplasm
Nucleotides
Fibroblasts
RNA

ASJC Scopus subject areas

  • General

Cite this

Hüttelmaier, S., Zenklusen, D., Lederer, M., Dictenberg, J., Lorenz, M., Meng, X., ... Singer, R. H. (2005). Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1. Nature, 438(7067), 512-515. https://doi.org/10.1038/nature04115

Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1. / Hüttelmaier, Stefan; Zenklusen, Daniel; Lederer, Marcell; Dictenberg, Jason; Lorenz, Mike; Meng, XiuHua; Bassell, Gary J.; Condeelis, John S.; Singer, Robert H.

In: Nature, Vol. 438, No. 7067, 24.11.2005, p. 512-515.

Research output: Contribution to journalArticle

Hüttelmaier, S, Zenklusen, D, Lederer, M, Dictenberg, J, Lorenz, M, Meng, X, Bassell, GJ, Condeelis, JS & Singer, RH 2005, 'Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1', Nature, vol. 438, no. 7067, pp. 512-515. https://doi.org/10.1038/nature04115
Hüttelmaier S, Zenklusen D, Lederer M, Dictenberg J, Lorenz M, Meng X et al. Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1. Nature. 2005 Nov 24;438(7067):512-515. https://doi.org/10.1038/nature04115
Hüttelmaier, Stefan ; Zenklusen, Daniel ; Lederer, Marcell ; Dictenberg, Jason ; Lorenz, Mike ; Meng, XiuHua ; Bassell, Gary J. ; Condeelis, John S. ; Singer, Robert H. / Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1. In: Nature. 2005 ; Vol. 438, No. 7067. pp. 512-515.
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