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Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex
We previously reported that Asunder (ASUN) is essential for recruitment of dynein motors to the nuclear envelope (NE) and nucleus–centrosome coupling at the onset of cell division in cultured human cells and Drosophila spermatocytes, although the mechanisms underlying this regulation remain unknown....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771956/ https://www.ncbi.nlm.nih.gov/pubmed/23904267 http://dx.doi.org/10.1091/mbc.E13-05-0254 |
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author | Jodoin, Jeanne N. Sitaram, Poojitha Albrecht, Todd R. May, Sarah B. Shboul, Mohammad Lee, Ethan Reversade, Bruno Wagner, Eric J. Lee, Laura A. |
author_facet | Jodoin, Jeanne N. Sitaram, Poojitha Albrecht, Todd R. May, Sarah B. Shboul, Mohammad Lee, Ethan Reversade, Bruno Wagner, Eric J. Lee, Laura A. |
author_sort | Jodoin, Jeanne N. |
collection | PubMed |
description | We previously reported that Asunder (ASUN) is essential for recruitment of dynein motors to the nuclear envelope (NE) and nucleus–centrosome coupling at the onset of cell division in cultured human cells and Drosophila spermatocytes, although the mechanisms underlying this regulation remain unknown. We also identified ASUN as a functional component of Integrator (INT), a multisubunit complex required for 3′-end processing of small nuclear RNAs. We now provide evidence that ASUN acts in the nucleus in concert with other INT components to mediate recruitment of dynein to the NE. Knockdown of other individual INT subunits in HeLa cells recapitulates the loss of perinuclear dynein in ASUN–small interfering RNA cells. Forced localization of ASUN to the cytoplasm via mutation of its nuclear localization sequence blocks its capacity to restore perinuclear dynein in both cultured human cells lacking ASUN and Drosophila asun spermatocytes. In addition, the levels of several INT subunits are reduced at G2/M when dynein is recruited to the NE, suggesting that INT does not directly mediate this step. Taken together, our data support a model in which a nuclear INT complex promotes recruitment of cytoplasmic dynein to the NE, possibly via a mechanism involving RNA processing. |
format | Online Article Text |
id | pubmed-3771956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-37719562013-11-30 Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex Jodoin, Jeanne N. Sitaram, Poojitha Albrecht, Todd R. May, Sarah B. Shboul, Mohammad Lee, Ethan Reversade, Bruno Wagner, Eric J. Lee, Laura A. Mol Biol Cell Articles We previously reported that Asunder (ASUN) is essential for recruitment of dynein motors to the nuclear envelope (NE) and nucleus–centrosome coupling at the onset of cell division in cultured human cells and Drosophila spermatocytes, although the mechanisms underlying this regulation remain unknown. We also identified ASUN as a functional component of Integrator (INT), a multisubunit complex required for 3′-end processing of small nuclear RNAs. We now provide evidence that ASUN acts in the nucleus in concert with other INT components to mediate recruitment of dynein to the NE. Knockdown of other individual INT subunits in HeLa cells recapitulates the loss of perinuclear dynein in ASUN–small interfering RNA cells. Forced localization of ASUN to the cytoplasm via mutation of its nuclear localization sequence blocks its capacity to restore perinuclear dynein in both cultured human cells lacking ASUN and Drosophila asun spermatocytes. In addition, the levels of several INT subunits are reduced at G2/M when dynein is recruited to the NE, suggesting that INT does not directly mediate this step. Taken together, our data support a model in which a nuclear INT complex promotes recruitment of cytoplasmic dynein to the NE, possibly via a mechanism involving RNA processing. The American Society for Cell Biology 2013-09-15 /pmc/articles/PMC3771956/ /pubmed/23904267 http://dx.doi.org/10.1091/mbc.E13-05-0254 Text en © 2013 Jodoin et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Jodoin, Jeanne N. Sitaram, Poojitha Albrecht, Todd R. May, Sarah B. Shboul, Mohammad Lee, Ethan Reversade, Bruno Wagner, Eric J. Lee, Laura A. Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex |
title | Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex |
title_full | Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex |
title_fullStr | Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex |
title_full_unstemmed | Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex |
title_short | Nuclear-localized Asunder regulates cytoplasmic dynein localization via its role in the Integrator complex |
title_sort | nuclear-localized asunder regulates cytoplasmic dynein localization via its role in the integrator complex |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771956/ https://www.ncbi.nlm.nih.gov/pubmed/23904267 http://dx.doi.org/10.1091/mbc.E13-05-0254 |
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