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Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux

TPX2 is a Ran-regulated spindle assembly factor that is required for kinetochore fiber formation and activation of the mitotic kinase Aurora A. TPX2 is enriched near spindle poles and is required near kinetochores, suggesting that it undergoes dynamic relocalization throughout mitosis. Using photoac...

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Detalles Bibliográficos
Autores principales: Ma, Nan, Tulu, U. S., Ferenz, Nick P., Fagerstrom, Carey, Wilde, Andrew, Wadsworth, Patricia
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836978/
https://www.ncbi.nlm.nih.gov/pubmed/20110350
http://dx.doi.org/10.1091/mbc.E09-07-0601
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author Ma, Nan
Tulu, U. S.
Ferenz, Nick P.
Fagerstrom, Carey
Wilde, Andrew
Wadsworth, Patricia
author_facet Ma, Nan
Tulu, U. S.
Ferenz, Nick P.
Fagerstrom, Carey
Wilde, Andrew
Wadsworth, Patricia
author_sort Ma, Nan
collection PubMed
description TPX2 is a Ran-regulated spindle assembly factor that is required for kinetochore fiber formation and activation of the mitotic kinase Aurora A. TPX2 is enriched near spindle poles and is required near kinetochores, suggesting that it undergoes dynamic relocalization throughout mitosis. Using photoactivation, we measured the movement of PA-GFP-TPX2 in the mitotic spindle. TPX2 moves poleward in the half-spindle and is static in the interzone and near spindle poles. Poleward transport of TPX2 is sensitive to inhibition of dynein or Eg5 and to suppression of microtubule flux with nocodazole or antibodies to Kif2a. Poleward transport requires the C terminus of TPX2, a domain that interacts with Eg5. Overexpression of TPX2 lacking this domain induced excessive microtubule formation near kinetochores, defects in spindle assembly and blocked mitotic progression. Our data support a model in which poleward transport of TPX2 down-regulates its microtubule nucleating activity near kinetochores and links microtubules generated at kinetochores to dynein for incorporation into the spindle.
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spelling pubmed-28369782010-05-30 Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux Ma, Nan Tulu, U. S. Ferenz, Nick P. Fagerstrom, Carey Wilde, Andrew Wadsworth, Patricia Mol Biol Cell Articles TPX2 is a Ran-regulated spindle assembly factor that is required for kinetochore fiber formation and activation of the mitotic kinase Aurora A. TPX2 is enriched near spindle poles and is required near kinetochores, suggesting that it undergoes dynamic relocalization throughout mitosis. Using photoactivation, we measured the movement of PA-GFP-TPX2 in the mitotic spindle. TPX2 moves poleward in the half-spindle and is static in the interzone and near spindle poles. Poleward transport of TPX2 is sensitive to inhibition of dynein or Eg5 and to suppression of microtubule flux with nocodazole or antibodies to Kif2a. Poleward transport requires the C terminus of TPX2, a domain that interacts with Eg5. Overexpression of TPX2 lacking this domain induced excessive microtubule formation near kinetochores, defects in spindle assembly and blocked mitotic progression. Our data support a model in which poleward transport of TPX2 down-regulates its microtubule nucleating activity near kinetochores and links microtubules generated at kinetochores to dynein for incorporation into the spindle. The American Society for Cell Biology 2010-03-15 /pmc/articles/PMC2836978/ /pubmed/20110350 http://dx.doi.org/10.1091/mbc.E09-07-0601 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Ma, Nan
Tulu, U. S.
Ferenz, Nick P.
Fagerstrom, Carey
Wilde, Andrew
Wadsworth, Patricia
Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux
title Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux
title_full Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux
title_fullStr Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux
title_full_unstemmed Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux
title_short Poleward Transport of TPX2 in the Mammalian Mitotic Spindle Requires Dynein, Eg5, and Microtubule Flux
title_sort poleward transport of tpx2 in the mammalian mitotic spindle requires dynein, eg5, and microtubule flux
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836978/
https://www.ncbi.nlm.nih.gov/pubmed/20110350
http://dx.doi.org/10.1091/mbc.E09-07-0601
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