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mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth

Cell motility requires strict spatiotemporal control of protein expression. During cell migration, mRNA localization and local translation in subcellular areas like the leading edge and protrusions are particularly advantageous for regulating the reorganization of the cytoskeleton. Fidgetin-Like 2 (...

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Autores principales: Birnbaum, Rayna, Biswas, Jeetayu, Singer, Robert H., Sharp, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153175/
https://www.ncbi.nlm.nih.gov/pubmed/37131812
http://dx.doi.org/10.1101/2023.04.17.537087
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author Birnbaum, Rayna
Biswas, Jeetayu
Singer, Robert H.
Sharp, David J.
author_facet Birnbaum, Rayna
Biswas, Jeetayu
Singer, Robert H.
Sharp, David J.
author_sort Birnbaum, Rayna
collection PubMed
description Cell motility requires strict spatiotemporal control of protein expression. During cell migration, mRNA localization and local translation in subcellular areas like the leading edge and protrusions are particularly advantageous for regulating the reorganization of the cytoskeleton. Fidgetin-Like 2 (FL2), a microtubule severing enzyme (MSE) that restricts migration and outgrowth, localizes to the leading edge of protrusions where it severs dynamic microtubules. FL2 is primarily expressed during development but in adulthood, is spatially upregulated at the leading edge minutes after injury. Here, we show mRNA localization and local translation in protrusions of polarized cells are responsible for FL2 leading edge expression after injury. The data suggests that the RNA binding protein IMP1 is involved in the translational regulation and stabilization of FL2 mRNA, in competition with the miRNA let-7. These data exemplify the role of local translation in microtubule network reorganization during migration and elucidate an unexplored MSE protein localization mechanism.
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spelling pubmed-101531752023-05-03 mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth Birnbaum, Rayna Biswas, Jeetayu Singer, Robert H. Sharp, David J. bioRxiv Article Cell motility requires strict spatiotemporal control of protein expression. During cell migration, mRNA localization and local translation in subcellular areas like the leading edge and protrusions are particularly advantageous for regulating the reorganization of the cytoskeleton. Fidgetin-Like 2 (FL2), a microtubule severing enzyme (MSE) that restricts migration and outgrowth, localizes to the leading edge of protrusions where it severs dynamic microtubules. FL2 is primarily expressed during development but in adulthood, is spatially upregulated at the leading edge minutes after injury. Here, we show mRNA localization and local translation in protrusions of polarized cells are responsible for FL2 leading edge expression after injury. The data suggests that the RNA binding protein IMP1 is involved in the translational regulation and stabilization of FL2 mRNA, in competition with the miRNA let-7. These data exemplify the role of local translation in microtubule network reorganization during migration and elucidate an unexplored MSE protein localization mechanism. Cold Spring Harbor Laboratory 2023-04-17 /pmc/articles/PMC10153175/ /pubmed/37131812 http://dx.doi.org/10.1101/2023.04.17.537087 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Birnbaum, Rayna
Biswas, Jeetayu
Singer, Robert H.
Sharp, David J.
mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth
title mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth
title_full mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth
title_fullStr mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth
title_full_unstemmed mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth
title_short mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth
title_sort mrna localization and local translation of the microtubule severing enzyme, fidgetin-like 2, in polarization, migration and outgrowth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153175/
https://www.ncbi.nlm.nih.gov/pubmed/37131812
http://dx.doi.org/10.1101/2023.04.17.537087
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