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Localization and translation of mRNA in dentrites and axons

Nature Reviews Neuroscience volume 2, pages 889–898 (2001)Cite this article

Key Points

  • Messenger RNAs and the structures needed for protein translation have been found in neuronal dendrites and axons. This article reviews the possible mechanisms for mRNA localization in neuronal processes, and the evidence for their translation, as well as the regulation and possible functional implications of dendritic translation.

  • Dendrites contain the structural machinery needed for protein translation. They also contain mRNAs, which can be amplified, identified and quantified. Different dendrites of a single neuron can contain different mRNAs, or the same mRNAs at different abundances. These mRNAs include those coding for neurotransmitter receptors, kinases and transcription factors.

  • Specific mRNAs are actively transported to the dendrites, and this transport can be altered by neuronal stimulation. It is unclear how mRNAs are targeted to dendrites, but there is evidence implicating the 3′- and 5′-untranslated regions of mRNAs in this process. RNA-binding proteins might be important for mRNA localization.

  • Translation of mRNAs into proteins occurs in dendrites, even when they are isolated from the cell body. It can be enhanced by stimulation with an agonist for metabotropic glutamate receptors or with neurotrophins, and seems to occur at specific, immobile locations in the dendrite. These sites are heterogeneous, with some showing linear translation and others showing exponential translation.

    • Stimulation-dependent protein translation in dendrites could have important functional consequences, possibly providing a mechanism for specific, activity-dependent changes in synaptic strength. Long-term plasticity in some neurons requires dendritic protein synthesis. Various models have been proposed in which local protein synthesis in dendrites could allow specific synaptic plasticity.

  • There is also evidence for mRNA localization and protein synthesis in axons. Much of this evidence comes from invertebrate axons, but it is clear that mRNAs are also found in vertebrate axons. There is, however, little evidence yet for axonal translation of mRNAs in vertebrates.

Abstract

The neurons of the brain extend axons and dendrites many hundreds of micrometres away from the cell body. The first electron microscope studies of these processes revealed that many of the structures that are found in the cell body are also present in dendrites. For example, particles resembling ribosomes and membrane structures like those of the endoplasmic reticulum (two structures that are important for protein synthesis) were seen in distal regions of dendrites, near synapses. Subsequent studies focused on identifying messenger RNAs in dendrites and providing evidence of dendritic protein synthesis. Transfection technologies have now been used to analyse translation within dendrites in response to pharmacological stimuli. These studies provide us with clues to the physiological role of the dendrite not just as a signal transducer, but also as a modulator of long-term synaptic efficacy.

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Figure 1: Electron-microscopic evidence for the existence of Golgi markers in neuronal dendrites.
Figure 2: In situ hybridization showing that MAP2 mRNA is localized in neuronal dendrites in tissue sections.
Figure 3: Time course of mRNA detection in dendritic growth cones in culture.
Figure 4: Movement of RNA-containing granules in dendrites of cultured neurons.
Figure 5: De novo protein synthesis in live dendrites correlates with ribosomal protein abundance.
Figure 6: Schematic of mRNA translational processes in dendrites.

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Acknowledgements

This work was funded by National Institutes of Health grants to J.E.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, 19104-6058, Pennsylvania, USA

    Christy Job & James Eberwine

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  1. Christy Job
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Correspondence to James Eberwine.

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DATABASES

FlyBase

Bicoid

Cyclin B

Nanos

GenBank

VG1

LocusLink

β-actin

Arc

BC1

BDNF

calcitonin-gene-related peptide

α-CaMKII

Cx26

Cx32

dendrin

EF-1α

FMRP

GAD65

GAP43

GluR2

glycine receptors

InsP3R

ligatin

MAP2

MBP

mGluR1

mGluR5

neurofilament light polypeptide

neurofilament medium polypeptide

neurogranin

neurotrophin 3

NGFR

NOS

odorant receptors

olfactory marker protein

oxytocin

prodynorphin

staufen

TGN38

translin

Trk

tubulin

vasopressin

FURTHER INFORMATION

dendrites

Glossary

PULSE–CHASE EXPERIMENTS

Experiments in which addition of a radioactive amino acid (pulse) is followed by non-labelled amino acid (chase), and the production of radioactive proteins from the amino-acid precursors is monitored.

CIS-ACTING ELEMENT

A regulatory genetic element located in the same DNA molecule as the gene being regulated.

SYNAPTOSOME

The presynaptic terminal isolated after subcellular fractionation. This structure retains the anatomical integrity of the terminal, and can take up, store and release neurotransmitters.

MYRISTOYLATION

The covalent attachment of a hydrophobic myristoyl group to the amino-terminal glycine residue of a nascent polypeptide.

MULTIPHOTON MICROSCOPY

A technique in which the intersection of distinct light sources is used to visualize objects. This method produces lower-energy fluorescent stimulation than confocal microscopy, resulting in less phototoxicity.

SYNAPTONEUROSOME

The presynaptic terminal isolated in conjunction with the postsynaptic spine after subcellular fractionation. This structure retains the anatomical integrity of the synapse.

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Job, C., Eberwine, J. Localization and translation of mRNA in dentrites and axons. Nat Rev Neurosci 2, 889–898 (2001). https://doi.org/10.1038/35104069

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