Cargando…

Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry

Recruitment of dynein motors to the nuclear surface is an essential step for nucleus–centrosome coupling in prophase. In cultured human cells, this dynein pool is anchored to nuclear pore complexes through RanBP2–Bicaudal D2 (BICD2) and Nup133– centromere protein F (CENP-F) networks. We previously r...

Descripción completa

Detalles Bibliográficos
Autores principales: Jodoin, Jeanne N., Shboul, Mohammad, Sitaram, Poojitha, Zein-Sabatto, Hala, Reversade, Bruno, Lee, Ethan, Lee, Laura A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521680/
https://www.ncbi.nlm.nih.gov/pubmed/23097494
http://dx.doi.org/10.1091/mbc.E12-07-0558
_version_ 1782252978917343232
author Jodoin, Jeanne N.
Shboul, Mohammad
Sitaram, Poojitha
Zein-Sabatto, Hala
Reversade, Bruno
Lee, Ethan
Lee, Laura A.
author_facet Jodoin, Jeanne N.
Shboul, Mohammad
Sitaram, Poojitha
Zein-Sabatto, Hala
Reversade, Bruno
Lee, Ethan
Lee, Laura A.
author_sort Jodoin, Jeanne N.
collection PubMed
description Recruitment of dynein motors to the nuclear surface is an essential step for nucleus–centrosome coupling in prophase. In cultured human cells, this dynein pool is anchored to nuclear pore complexes through RanBP2–Bicaudal D2 (BICD2) and Nup133– centromere protein F (CENP-F) networks. We previously reported that the asunder (asun) gene is required in Drosophila spermatocytes for perinuclear dynein localization and nucleus–centrosome coupling at G2/M of male meiosis. We show here that male germline expression of mammalian Asunder (ASUN) protein rescues asun flies, demonstrating evolutionary conservation of function. In cultured human cells, we find that ASUN down-regulation causes reduction of perinuclear dynein in prophase of mitosis. Additional defects after loss of ASUN include nucleus–centrosome uncoupling, abnormal spindles, and multinucleation. Coimmunoprecipitation and overlapping localization patterns of ASUN and lissencephaly 1 (LIS1), a dynein adaptor, suggest that ASUN interacts with dynein in the cytoplasm via LIS1. Our data indicate that ASUN controls dynein localization via a mechanism distinct from that of either BICD2 or CENP-F. We present a model in which ASUN promotes perinuclear enrichment of dynein at G2/M that facilitates BICD2- and CENP-F-mediated anchoring of dynein to nuclear pore complexes.
format Online
Article
Text
id pubmed-3521680
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-35216802013-03-02 Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry Jodoin, Jeanne N. Shboul, Mohammad Sitaram, Poojitha Zein-Sabatto, Hala Reversade, Bruno Lee, Ethan Lee, Laura A. Mol Biol Cell Articles Recruitment of dynein motors to the nuclear surface is an essential step for nucleus–centrosome coupling in prophase. In cultured human cells, this dynein pool is anchored to nuclear pore complexes through RanBP2–Bicaudal D2 (BICD2) and Nup133– centromere protein F (CENP-F) networks. We previously reported that the asunder (asun) gene is required in Drosophila spermatocytes for perinuclear dynein localization and nucleus–centrosome coupling at G2/M of male meiosis. We show here that male germline expression of mammalian Asunder (ASUN) protein rescues asun flies, demonstrating evolutionary conservation of function. In cultured human cells, we find that ASUN down-regulation causes reduction of perinuclear dynein in prophase of mitosis. Additional defects after loss of ASUN include nucleus–centrosome uncoupling, abnormal spindles, and multinucleation. Coimmunoprecipitation and overlapping localization patterns of ASUN and lissencephaly 1 (LIS1), a dynein adaptor, suggest that ASUN interacts with dynein in the cytoplasm via LIS1. Our data indicate that ASUN controls dynein localization via a mechanism distinct from that of either BICD2 or CENP-F. We present a model in which ASUN promotes perinuclear enrichment of dynein at G2/M that facilitates BICD2- and CENP-F-mediated anchoring of dynein to nuclear pore complexes. The American Society for Cell Biology 2012-12-15 /pmc/articles/PMC3521680/ /pubmed/23097494 http://dx.doi.org/10.1091/mbc.E12-07-0558 Text en © 2012 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 BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Jodoin, Jeanne N.
Shboul, Mohammad
Sitaram, Poojitha
Zein-Sabatto, Hala
Reversade, Bruno
Lee, Ethan
Lee, Laura A.
Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry
title Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry
title_full Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry
title_fullStr Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry
title_full_unstemmed Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry
title_short Human Asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry
title_sort human asunder promotes dynein recruitment and centrosomal tethering to the nucleus at mitotic entry
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521680/
https://www.ncbi.nlm.nih.gov/pubmed/23097494
http://dx.doi.org/10.1091/mbc.E12-07-0558
work_keys_str_mv AT jodoinjeannen humanasunderpromotesdyneinrecruitmentandcentrosomaltetheringtothenucleusatmitoticentry
AT shboulmohammad humanasunderpromotesdyneinrecruitmentandcentrosomaltetheringtothenucleusatmitoticentry
AT sitarampoojitha humanasunderpromotesdyneinrecruitmentandcentrosomaltetheringtothenucleusatmitoticentry
AT zeinsabattohala humanasunderpromotesdyneinrecruitmentandcentrosomaltetheringtothenucleusatmitoticentry
AT reversadebruno humanasunderpromotesdyneinrecruitmentandcentrosomaltetheringtothenucleusatmitoticentry
AT leeethan humanasunderpromotesdyneinrecruitmentandcentrosomaltetheringtothenucleusatmitoticentry
AT leelauraa humanasunderpromotesdyneinrecruitmentandcentrosomaltetheringtothenucleusatmitoticentry