Cited by 264Nerve injury and regenerationAxon Guidance and Neuronal SignalingRNA and protein synthesis mechanisms

Local translation of extranuclear lamin B promotes axon maintenance

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Yoon, Byung C., Jung, Hosung, Dwivedy, Asha, O'Hare, Catherine M., Zivraj, Krishna H., Holt, Christine E.·2012·Cell

Abstract

Local protein synthesis plays a key role in regulating stimulus-induced responses in dendrites and axons. Recent genome-wide studies have revealed that thousands of different transcripts reside in these distal neuronal compartments, but identifying those with functionally significant roles presents a challenge. We performed an unbiased screen to look for stimulus-induced, protein synthesis-dependent changes in the proteome of Xenopus retinal ganglion cell (RGC) axons. The intermediate filament protein lamin B2 (LB2), normally associated with the nuclear membrane, was identified as an unexpected major target. Axonal ribosome immunoprecipitation confirmed translation of lb2 mRNA in vivo. Inhibition of lb2 mRNA translation in axons in vivo does not affect guidance but causes axonal degeneration. Axonal LB2 associates with mitochondria, and LB2-deficient axons exhibit mitochondrial dysfunction and defects in axonal transport. Our results thus suggest that axonally synthesized lamin B plays a crucial role in axon maintenance by promoting mitochondrial function.

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Crossref · 10.1016/j.cell.2011.11.064

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  • In dopaminergic neurons and retinal ganglion cell growth cones, translation of nuclear-encoded mitochondrial mRNAs commonly occurs after homeoprotein capture.

    “Indeed, translation of nuclear-encoded mitochondrial mRNAs commonly follows homeoprotein capture by dopaminergic neurons or retinal ganglion cell growth cones (Alvarez-Fischer et al., 2011; Stettler et al., 2012; Yoon et al., 2012).”

    From Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity (2013) · cites this paper as Yoon et al., 2012

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Research works printed but not linked: 8

  1. Campbell, D.S., and Holt, C.E. (2001). Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation. Neuron 32, 1013–1026. 11754834
  2. Chien, C.B., Rosenthal, D.E., Harris, W.A., and Holt, C.E. (1993). Navigational errors made by growth cones without filopodia in the embryonic Xenopus brain. Neuron 11, 237–251. 8352941
  3. Drinjakovic, J., Jung, H., Campbell, D.S., Strochlic, L., Dwivedy, A., and Holt, C.E. (2010). E3 ligase Nedd4 promotes axon branching by downregulating PTEN. Neuron 65, 341–357. PMC2862300 20159448
  4. Falk, J., Drinjakovic, J., Leung, K.M., Dwivedy, A., Regan, A.G., Piper, M., and Holt, C.E. (2007). Electroporation of cDNA/morpholinos to targeted areas of embryonic CNS in Xenopus. BMC Dev. Biol. 7, 107. PMC2147031 17900342
  5. Heiman, M., Schaefer, A., Gong, S., Peterson, J.D., Day, M., Ramsey, K.E., Suárez-Fariñas, M., Schwarz, C., Stephan, D.A., Surmeier, D.J., et al. (2008). A translational profiling approach for the molecular characterization of CNS cell types. Cell 135, 738–748. PMC2696821 19013281
  6. Holt, C.E. (1984). Does timing of axon outgrowth influence initial retinotectal topography in Xenopus? J. Neurosci. 4, 1130–1152. PMC6564775 6325604
  7. Piper, M., Anderson, R., Dwivedy, A., Weinl, C., van Horck, F., Leung, K.M., Cogill, E., and Holt, C. (2006). Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth cones. Neuron 49, 215–228. PMC3689199 16423696
  8. Zolessi, F.R., Poggi, L., Wilkinson, C.J., Chien, C.B., and Harris, W.A. (2006). Polarization and orientation of retinal ganglion cells in vivo. Neural Dev. 1, 2. PMC1636330 17147778

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Authors
Yoon, B. C., Jung, H., Dwivedy, A., O'Hare, C. M., Zivraj, K. H., & Holt, C. E.
Affiliations
University of Cambridge (GB)
Corresponding author
Holt, Christine E.
Venue
Cell
Publisher
Elsevier BV
Published
2012-02
Volume
148
Issue
4
Pages
752-764
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2089419574
Cited by
263
References
74
Citations by year
2026: 7 · 2025: 8 · 2024: 11 · 2023: 10 · 2022: 22 · 2021: 17 · 2020: 24 · 2019: 17 · 2018: 21 · 2017: 17 · 2016: 25 · 2015: 18 · 2014: 21 · 2013: 26 · 2012: 19
FWCI
11.20
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders
Wellcome Trust (085314/Z/08/Z, 085314)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
lamin B2, axon maintenance, local protein synthesis, axonal translation, retinal ganglion cells, axonal degeneration, mitochondrial dysfunction, axonal transport, intermediate filaments, Xenopus, axon guidance
MeSH terms
Animals, Axons, Axonal Transport, Embryo, Nonmammalian, Mitochondria, Retinal Ganglion Cells, Protein Biosynthesis, Xenopus laevis, Lamin Type B

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