Cargando…

RanGTP and CLASP1 cooperate to position the mitotic spindle

Accurate positioning of the mitotic spindle is critical to ensure proper distribution of chromosomes during cell division. The small GTPase Ran, which regulates a variety of processes throughout the cell cycle, including interphase nucleocytoplasmic transport and mitotic spindle assembly, was recent...

Descripción completa

Detalles Bibliográficos
Autores principales: Bird, Stephen L., Heald, Rebecca, Weis, Karsten
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/PMC3744954/
https://www.ncbi.nlm.nih.gov/pubmed/23783028
http://dx.doi.org/10.1091/mbc.E13-03-0150
_version_ 1782280664798724096
author Bird, Stephen L.
Heald, Rebecca
Weis, Karsten
author_facet Bird, Stephen L.
Heald, Rebecca
Weis, Karsten
author_sort Bird, Stephen L.
collection PubMed
description Accurate positioning of the mitotic spindle is critical to ensure proper distribution of chromosomes during cell division. The small GTPase Ran, which regulates a variety of processes throughout the cell cycle, including interphase nucleocytoplasmic transport and mitotic spindle assembly, was recently shown to also control spindle alignment. Ran is required for the correct cortical localization of LGN and nuclear-mitotic apparatus protein (NuMA), proteins that generate pulling forces on astral microtubules (MTs) through cytoplasmic dynein. Here we use importazole, a small-molecule inhibitor of RanGTP/importin-β function, to study the role of Ran in spindle positioning in human cells. We find that importazole treatment results in defects in astral MT dynamics, as well as in mislocalization of LGN and NuMA, leading to misoriented spindles. Of interest, importazole-induced spindle-centering defects can be rescued by nocodazole treatment, which depolymerizes astral MTs, or by overexpression of CLASP1, which does not restore proper LGN and NuMA localization but stabilizes astral MT interactions with the cortex. Together our data suggest a model for mitotic spindle positioning in which RanGTP and CLASP1 cooperate to align the spindle along the long axis of the dividing cell.
format Online
Article
Text
id pubmed-3744954
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-37449542013-10-30 RanGTP and CLASP1 cooperate to position the mitotic spindle Bird, Stephen L. Heald, Rebecca Weis, Karsten Mol Biol Cell Articles Accurate positioning of the mitotic spindle is critical to ensure proper distribution of chromosomes during cell division. The small GTPase Ran, which regulates a variety of processes throughout the cell cycle, including interphase nucleocytoplasmic transport and mitotic spindle assembly, was recently shown to also control spindle alignment. Ran is required for the correct cortical localization of LGN and nuclear-mitotic apparatus protein (NuMA), proteins that generate pulling forces on astral microtubules (MTs) through cytoplasmic dynein. Here we use importazole, a small-molecule inhibitor of RanGTP/importin-β function, to study the role of Ran in spindle positioning in human cells. We find that importazole treatment results in defects in astral MT dynamics, as well as in mislocalization of LGN and NuMA, leading to misoriented spindles. Of interest, importazole-induced spindle-centering defects can be rescued by nocodazole treatment, which depolymerizes astral MTs, or by overexpression of CLASP1, which does not restore proper LGN and NuMA localization but stabilizes astral MT interactions with the cortex. Together our data suggest a model for mitotic spindle positioning in which RanGTP and CLASP1 cooperate to align the spindle along the long axis of the dividing cell. The American Society for Cell Biology 2013-08-15 /pmc/articles/PMC3744954/ /pubmed/23783028 http://dx.doi.org/10.1091/mbc.E13-03-0150 Text en © 2013 Bird 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
Bird, Stephen L.
Heald, Rebecca
Weis, Karsten
RanGTP and CLASP1 cooperate to position the mitotic spindle
title RanGTP and CLASP1 cooperate to position the mitotic spindle
title_full RanGTP and CLASP1 cooperate to position the mitotic spindle
title_fullStr RanGTP and CLASP1 cooperate to position the mitotic spindle
title_full_unstemmed RanGTP and CLASP1 cooperate to position the mitotic spindle
title_short RanGTP and CLASP1 cooperate to position the mitotic spindle
title_sort rangtp and clasp1 cooperate to position the mitotic spindle
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744954/
https://www.ncbi.nlm.nih.gov/pubmed/23783028
http://dx.doi.org/10.1091/mbc.E13-03-0150
work_keys_str_mv AT birdstephenl rangtpandclasp1cooperatetopositionthemitoticspindle
AT healdrebecca rangtpandclasp1cooperatetopositionthemitoticspindle
AT weiskarsten rangtpandclasp1cooperatetopositionthemitoticspindle