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Local Translation of Extranuclear Lamin B Promotes Axon Maintenance

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...

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Autores principales: Yoon, Byung C., Jung, Hosung, Dwivedy, Asha, O'Hare, Catherine M., Zivraj, Krishna H., Holt, Christine E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314965/
https://www.ncbi.nlm.nih.gov/pubmed/22341447
http://dx.doi.org/10.1016/j.cell.2011.11.064
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author Yoon, Byung C.
Jung, Hosung
Dwivedy, Asha
O'Hare, Catherine M.
Zivraj, Krishna H.
Holt, Christine E.
author_facet Yoon, Byung C.
Jung, Hosung
Dwivedy, Asha
O'Hare, Catherine M.
Zivraj, Krishna H.
Holt, Christine E.
author_sort Yoon, Byung C.
collection PubMed
description 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 ofXenopus 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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spelling pubmed-33149652012-04-11 Local Translation of Extranuclear Lamin B Promotes Axon Maintenance Yoon, Byung C. Jung, Hosung Dwivedy, Asha O'Hare, Catherine M. Zivraj, Krishna H. Holt, Christine E. Cell Article 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 ofXenopus 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. Cell Press 2012-02-17 /pmc/articles/PMC3314965/ /pubmed/22341447 http://dx.doi.org/10.1016/j.cell.2011.11.064 Text en © 2012 ELL & Excerpta Medica. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Yoon, Byung C.
Jung, Hosung
Dwivedy, Asha
O'Hare, Catherine M.
Zivraj, Krishna H.
Holt, Christine E.
Local Translation of Extranuclear Lamin B Promotes Axon Maintenance
title Local Translation of Extranuclear Lamin B Promotes Axon Maintenance
title_full Local Translation of Extranuclear Lamin B Promotes Axon Maintenance
title_fullStr Local Translation of Extranuclear Lamin B Promotes Axon Maintenance
title_full_unstemmed Local Translation of Extranuclear Lamin B Promotes Axon Maintenance
title_short Local Translation of Extranuclear Lamin B Promotes Axon Maintenance
title_sort local translation of extranuclear lamin b promotes axon maintenance
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314965/
https://www.ncbi.nlm.nih.gov/pubmed/22341447
http://dx.doi.org/10.1016/j.cell.2011.11.064
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