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  • Review Article
  • Published:

Dendritic mRNA: transport, translation and function

Nature Reviews Neuroscience volume 8, pages 776–789 (2007)Cite this article

Key Points

  • Dendritic protein synthesis involves the coordination of mRNA transport, localization and translation. These steps are modulated by synaptic activity and by neurotransmitters such as glutamate, brain-derived neurotrophic factor, dopamine and others.

  • Dendritic mRNA translation provides a mechanism for local-protein-synthesis-dependent modification of neuronal structure and function. Stable forms of long-term potentiation (LTP) and long-term depression (LTD) require dendritic protein synthesis.

  • RNAs are sorted into large ribonucleoprotein particles and transported to dendrites along microtubules. Stored RNAs are kept translationally dormant by sequence-specific RNA-binding proteins and microRNAs.

  • Synaptic activity and neurotransmitter signalling regulate global and mRNA-specific translation in dendrites. Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) and eukaryotic translation elongation factor F2 (eEF2) regulates global enhancement of translation initiation and arrest of peptide chain elongation, respectively.

  • RNA-binding proteins and microRNAs have emerged as the principle regulators of mRNA-specific translation; neurotransmitters can stimulate local protein synthesis by inhibiting these inhibitors and, thus, de-repressing translation.

  • Dendritic transport and local synthesis of the immediate early gene product Arc (also known as Arg3.1) is necessary for the local expansion of the actin cytoskeleton that underlies LTP consolidation in the dentate gyrus. Cytoplasmic-polyadenylation-element-binding protein 1 (CPEB1)-mediated translation in Purkinje neurons of the cerebellum is necessary for LTD, motor learning and dendritic synthesis of insulin receptor substrate p53 (IRSp53), an important regulator of actin dynamics.

  • Dendritically synthesized proteins are implicated in various functions, including the regulation of actin dynamics, glutamate receptor trafficking and modulation of the extracellular matrix.

Abstract

Many cellular functions require the synthesis of a specific protein or functional cohort of proteins at a specific time and place in the cell. Local protein synthesis in neuronal dendrites is essential for understanding how neural activity patterns are transduced into persistent changes in synaptic connectivity during cortical development, memory storage and other long-term adaptive brain responses. Regional and temporal changes in protein levels are commonly coordinated by an asymmetric distribution of mRNAs. This Review attempts to integrate current knowledge of dendritic mRNA transport, storage and translation, placing particular emphasis on the coordination of regulation and function during activity-dependent synaptic plasticity in the adult mammalian brain.

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Figure 1: Proposed model for mRNA translation in neuronal dendrites.
Figure 2: Translation control in dendrites.
Figure 3: A model of Arc-dependent LTP consolidation in the dentate gyrus.
Figure 4: A proposed model for the role of CPEB1-mediated protein synthesis in cerebellar LTD.
Figure 5: Predicted functional synergy of dendritically synthesized proteins.

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Acknowledgements

We thank members of the Bramham and Wells laboratories for discussions. C.R.B. is supported by the Norwegian Research Council, the EU Biotechnology Program (BIO4-CT98-0333) and the Helse-Bergen Health Organization. D.G.W. is supported by the Ellison Medical Foundation and the National Institute of Mental Health. We apologize for the fact that, owing to space constraints, not all relevant papers could be cited.

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  1. Department of Biomedicine and Bergen Mental Health Research Center, University of Bergen, Jonas Lies vei 91, Bergen, N-5009, Norway

    Clive R. Bramham

  2. Department of Molecular, Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, 06520-8103, Connecticut, USA

    David G. Wells

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Glossary

Postsynaptic density

(PSD). An electron dense complex that is located at the synaptic membrane of a postsynaptic cell. The PSD contains transmembrane proteins, such as neurotransmitter receptors, as well as intracellular signalling molecules.

Ribonucleoprotein particle

(RNP). A transport granule that contains mRNA, mRNA-binding proteins, motor proteins and small, non-coding RNA (also known as microRNA).

Stress granule

A dense cytosolic protein and RNA aggregation that appears under conditions of cellular stress. The RNA molecules are thought to be stalled translation pre-initiation complexes.

Processing body

A cytoplasmic structure that is thought to be the site of mRNA degradation.

Kinesins

Molecular motor proteins that transport cargoes in one direction along microtubules. For movement in the opposite direction, another motor protein, dynein, is used.

Heterogeneous nuclear ribonucleoproteins

(hnRNPs). A large family of RNA-binding proteins that are involved in RNA regulation and metabolism. Examples of hnRNPs that have been implicated in dendritic mRNA processing include ZBP1, FMRP and hnRNP A2.

Polyribosome

A functional unit of protein synthesis comprised of several ribosomes attached along the length of an mRNA molecule.

Synaptodendrosome

A biochemical fraction that is enriched in pinched-off, resealed axon terminals that are connected to pinched-off, resealed dendritic spines. They are commonly prepared by a two-step ultracentrifugation through a sucrose gradient.

Synaptoneurosome

A biochemical fraction that is qualitatively similar to a synaptodendrosome but which is prepared by low-speed centrifugation and filtration.

RNA interference complex

(RISC). A complex of proteins that is involved in silencing target mRNAs.

Synaptic tagging

A process by which synaptic activity evokes a transient synapse-specific change that allows the synapse to capture proteins or mRNAs that are needed for stable LTP and LTD.

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Bramham, C., Wells, D. Dendritic mRNA: transport, translation and function. Nat Rev Neurosci 8, 776–789 (2007). https://doi.org/10.1038/nrn2150

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