Protein synthesis within neuronal growth cones

Davis, Loyal; Dou, Ping; DeWit, M; Kater, Stanley B.

doi:10.1523/jneurosci.12-12-04867.1992

Cited by 77 publications

(53 citation statements)

References 29 publications

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“…While neurites at this stage have not yet differentiated into axons or dendrites, there is little doubt that young growth cones have the capacity to synthesize protein. Indeed, the detection of polysomes by electron microscopy (16) and the incorporation of radiolabeled amino acids into protein into isolated growth cones (15) demonstrate that translation does occur in this structure. Moreover, axon turning in vitro in response to exogenous cures also requires protein synthesis, although it is not known if this takes place in the growth cone, the axon shaft, or both (69).…”

Section: Discussionmentioning

confidence: 99%

Translational Control by Neuroguidin, a Eukaryotic Initiation Factor 4E and CPEB Binding Protein

Jung

Lorenz

Richter

2006

Molecular and Cellular Biology

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CPEB-mediated translation is important in early development and neuronal synaptic plasticity. Here, we describe a new eukaryotic initiation factor 4E (eIF4E) binding protein, Neuroguidin (Ngd), and its interaction with CPEB. In the mammalian nervous system, Ngd is detected as puncta in axons and dendrites and in growth cones and filopodia. Ngd contains three motifs that resemble those present in eIF4G, 4EBP, Cup, and Maskin, all of which are eIF4E binding proteins. Ngd binds eIF4E directly, and all three motifs must be deleted to abrogate the interaction between these two proteins. In injected Xenopus oocytes, Ngd binds CPEB and, most importantly, represses translation in a cytoplasmic polyadenylation element (CPE)-dependent manner. In Xenopus embryos, Ngd is found in both neural tube and neural crest cells. The injection of morpholinocontaining antisense oligonucleotides directed against ngd mRNA disrupts neural tube closure and neural crest migration; however, the wild-type phenotype is restored by the injection of a rescuing ngd mRNA. These data suggest that Ngd guides neural development by regulating the translation of CPE-containing mRNAs.

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Section: Discussionmentioning

confidence: 99%

Translational Control by Neuroguidin, a Eukaryotic Initiation Factor 4E and CPEB Binding Protein

Jung

Lorenz

Richter

2006

Molecular and Cellular Biology

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“…The existence of cytoplasmic protein synthesis in mammalian nerve endings is also indirectly suggested by the existence of a translation system in growth cones (66,190). In a number of experiments, this system has been shown to play an essential role in axon guidance during development (37,42,204,231,332,333).…”

Section: B Nerve Terminalsmentioning

confidence: 99%

Local Gene Expression in Axons and Nerve Endings: The Glia-Neuron Unit

Giuditta¹,

Chun²,

Eyman³

et al. 2008

Physiological Reviews

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Neurons have complex and often extensively elongated processes. This unique cell morphology raises the problem of how remote neuronal territories are replenished with proteins. For a long time, axonal and presynaptic proteins were thought to be exclusively synthesized in the cell body, which delivered them to peripheral sites by axoplasmic transport. Despite this early belief, protein has been shown to be synthesized in axons and nerve terminals, substantially alleviating the trophic burden of the perikaryon. This observation raised the question of the cellular origin of the peripheral RNAs involved in protein synthesis. The synthesis of these RNAs was initially attributed to the neuron soma almost by default. However, experimental data and theoretical considerations support the alternative view that axonal and presynaptic RNAs are also transcribed in the flanking glial cells and transferred to the axon domain of mature neurons. Altogether, these data suggest that axons and nerve terminals are served by a distinct gene expression system largely independent of the neuron cell body. Such a local system would allow the neuron periphery to respond promptly to environmental stimuli. This view has the theoretical merit of extending to axons and nerve terminals the marginalized concept of a glial supply of RNA (and protein) to the neuron cell body. Most long-term plastic changes requiring de novo gene expression occur in these domains, notably in presynaptic endings, despite their intrinsic lack of transcriptional capacity. This review enlightens novel perspectives on the biology and pathobiology of the neuron by critically reviewing these issues.

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“…Localized protein synthesis in dendrites is a well-accepted mechanism that that can be regulated by neurotransmitters and trophic factors (Steward, 2002). Evidence for protein synthesis in axons was initially provided from studies in invertebrates (Capano et al, 1987;Giuditta et al, 1991;Davis et al, 1992;Chun et al, 1996;van Minnen et al, 1997). Subsequent work showed that developing vertebrate axons contain mRNAs and actively synthesize proteins (Olink-Coux and Hollenbeck, 1996;Bassell et al, 1998;Eng et al, 1999;Zhang et al, 1999;Aronov et al, 2001;Campbell and Holt, 2001; Lee and Hollenbeck, 2003).…”

Section: Introductionmentioning

confidence: 99%

Differential Transport and Local Translation of Cytoskeletal, Injury-Response, and Neurodegeneration Protein mRNAs in Axons

Willis¹,

Li²,

Zheng³

et al. 2005

J. Neurosci.

360

391

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Recent studies have begun to focus on the signals that regulate axonal protein synthesis and the functional significance of localized protein synthesis. However, identification of proteins that are synthesized in mammalian axons has been mainly based on predictions. Here, we used axons purified from cultures of injury-conditioned adult dorsal root ganglion (DRG) neurons and proteomics methodology to identify axonally synthesized proteins. Reverse transcription (RT)-PCR from axonal preparations was used to confirm that the mRNA for each identified protein extended into the DRG axons. Proteins and the encoding mRNAs for the cytoskeletal proteins ␤-actin, peripherin, vimentin, ␥-tropomyosin 3, and cofilin 1 were present in the axonal preparations. In addition to the cytoskeletal elements, several heat shock proteins (HSP27, HSP60, HSP70, grp75, ␣B crystallin), resident endoplasmic reticulum (ER) proteins (calreticulin, grp78/BiP, ERp29), proteins associated with neurodegenerative diseases (ubiquitin C-terminal hydrolase L1, rat ortholog of human DJ-1/Park7, ␥-synuclein, superoxide dismutase 1), anti-oxidant proteins (peroxiredoxins 1 and 6), and metabolic proteins (e.g., phosphoglycerate kinase 1 (PGK 1), ␣ enolase, aldolase C/Zebrin II) were included among the axonally synthesized proteins. Detection of the mRNAs encoding each of the axonally synthesized proteins identified by mass spectrometry in the axonal compartment indicates that the DRG axons have the potential to synthesize a complex population of proteins. Local treatment of the DRG axons with NGF or BDNF increased levels of cytoskeletal mRNAs into the axonal compartment by twofold to fivefold but had no effect on levels of the other axonal mRNAs studied. Neurotrophins selectively increased transport of ␤-actin, peripherin, and vimentin mRNAs from the cell body into the axons rather than changing transcription or mRNA survival in the axonal compartment.

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Protein synthesis within neuronal growth cones

Cited by 77 publications

References 29 publications

Translational Control by Neuroguidin, a Eukaryotic Initiation Factor 4E and CPEB Binding Protein

Translational Control by Neuroguidin, a Eukaryotic Initiation Factor 4E and CPEB Binding Protein

Local Gene Expression in Axons and Nerve Endings: The Glia-Neuron Unit

Differential Transport and Local Translation of Cytoskeletal, Injury-Response, and Neurodegeneration Protein mRNAs in Axons

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