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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....

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Autores principales: Jodoin, Jeanne N., Sitaram, Poojitha, Albrecht, Todd R., May, Sarah B., Shboul, Mohammad, Lee, Ethan, Reversade, Bruno, Wagner, Eric J., Lee, Laura A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
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.
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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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