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Local Translation of Extranuclear Lamin B Promotes Axon Maintenance
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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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“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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Metadata
- 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)
- PMC
- PMC3314965
- 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
- hybrid
- doi.org
- Licence
- 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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